@article{katz_battle_vaeth_2025, title={The Evolution of CMGH as The Basic Research Journal in Gastroenterology and Hepatology: "H" is for "Home "}, volume={19}, ISSN={["2352-345X"]}, DOI={10.1016/j.jcmgh.2024.101450}, number={3}, journal={CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY}, author={Katz, Jonathan P. and Battle, Michele A. and Vaeth, Alexander M.}, year={2025} }
 @article{battle_katz_2024, title={<i>CMGH:</i> Evolving to Advance Gastroenterology and Hepatology Research}, volume={18}, ISSN={["2352-345X"]}, DOI={10.1016/j.jcmgh.2024.05.001}, number={1}, journal={CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY}, author={Battle, Michele A. and Katz, Jonathan P.}, year={2024}, pages={163–163} }
 @article{franklin_battle_2023, title={A Balancing Act: GRHL3 Limits WNT Signaling to Promote Tissue Homeostasis in the Esophageal Epithelium}, volume={15}, ISSN={2352-345X}, url={http://dx.doi.org/10.1016/j.jcmgh.2023.01.011}, DOI={10.1016/j.jcmgh.2023.01.011}, number={5}, journal={Cellular and Molecular Gastroenterology and Hepatology}, publisher={Elsevier BV}, author={Franklin, Olivia D. and Battle, Michele A.}, year={2023}, pages={1247–1248} }
 @article{stabenau_samuels_lam_mathison_wells_altman_battle_johnston_2022, title={Pepsinogen/Proton Pump Co‐Expression in Barrett's Esophageal Cells Induces <scp>Cancer‐Associated</scp> Changes}, volume={133}, ISSN={0023-852X 1531-4995}, url={http://dx.doi.org/10.1002/lary.30109}, DOI={10.1002/lary.30109}, abstractNote={Educational Objective At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus. Objective Barrett's esophagus (BE) is a well‐known risk factor for esophageal adenocarcinoma (EAC). Gastric H + /K + ATPase proton pump and pepsin expression has been demonstrated in some cases of BE; however, the contribution of local pepsin and proton pump expression to carcinogenesis is unknown. In this study, RNA sequencing was used to examine global transcriptomic changes in a BE cell line ectopically expressing pepsinogen and/or gastric H + /K + ATPase proton pumps. Study Design In vitro translational. Methods BAR‐T, a human BE cell line devoid of expression of pepsinogen or proton pumps, was transduced by lentivirus‐encoding pepsinogen ( PGA5 ) and/or gastric proton pump subunits ( ATP4A , ATP4B ). Changes relative to the parental line were assessed by RNA sequencing. Results Top canonical pathways associated with protein‐coding genes differentially expressed in pepsinogen and/or proton pump expressing BAR‐T cells included those involved in the tumor microenvironment and epithelial–mesenchymal transition. Top upstream regulators of coding transcripts included TGFB1 and ERBB2, which are associated with the pathogenesis and prognosis of BE and EAC. Top upstream regulators of noncoding transcripts included p300‐CBP, I‐BET‐151, and CD93, which have previously described associations with EAC or carcinogenesis. The top associated disease of both coding and noncoding transcripts was cancer. Conclusions These data support the carcinogenic potential of pepsin and proton pump expression in BE and reveal molecular pathways affected by their expression. Further study is warranted to investigate the role of these pathways in carcinogenesis associated with BE. Level of Evidence NA Laryngoscope , 133:59–69, 2023}, number={1}, journal={The Laryngoscope}, publisher={Wiley}, author={Stabenau, Kaleigh A. and Samuels, Tina L. and Lam, Tina K. and Mathison, Angela J. and Wells, Clive and Altman, Kenneth W. and Battle, Michele A. and Johnston, Nikki}, year={2022}, month={Mar}, pages={59–69} }
 @article{ramadan_wouters_van neerven_de groot_garcia_muncan_franklin_battle_carlson_leach_et al._2022, title={The extracellular matrix controls stem cell specification and crypt morphology in the developing and adult mouse gut}, volume={11}, ISSN={2046-6390}, url={http://dx.doi.org/10.1242/bio.059544}, DOI={10.1242/bio.059544}, abstractNote={ABSTRACT The rapid renewal of the epithelial gut lining is fuelled by stem cells that reside at the base of intestinal crypts. The signal transduction pathways and morphogens that regulate intestinal stem cell self-renewal and differentiation have been extensively characterised. In contrast, although extracellular matrix (ECM) components form an integral part of the intestinal stem cell niche, their direct influence on the cellular composition is less well understood. We set out to systematically compare the effect of two ECM classes, the interstitial matrix and the basement membrane, on the intestinal epithelium. We found that both collagen I and laminin-containing cultures allow growth of small intestinal epithelial cells with all cell types present in both cultures, albeit at different ratios. The collagen cultures contained a subset of cells enriched in fetal-like markers. In contrast, laminin increased Lgr5+ stem cells and Paneth cells, and induced crypt-like morphology changes. The transition from a collagen culture to a laminin culture resembled gut development in vivo. The dramatic ECM remodelling was accompanied by a local expression of the laminin receptor ITGA6 in the crypt-forming epithelium. Importantly, deletion of laminin in the adult mouse resulted in a marked reduction of adult intestinal stem cells. Overall, our data support the hypothesis that the formation of intestinal crypts is induced by an increased laminin concentration in the ECM.}, number={12}, journal={Biology Open}, publisher={The Company of Biologists}, author={Ramadan, Rana and Wouters, Valérie M. and van Neerven, Sanne M. and de Groot, Nina E. and Garcia, Tania Martins and Muncan, Vanessa and Franklin, Olivia D. and Battle, Michelle and Carlson, Karen Sue and Leach, Joshua and et al.}, year={2022}, month={Nov} }
 @article{delaforest_kohlnhofer_franklin_stavniichuk_thompson_pulakanti_rao_battle_2021, title={GATA4 Controls Epithelial Morphogenesis in the Developing Stomach to Promote Establishment of Glandular Columnar Epithelium}, volume={12}, ISSN={2352-345X}, url={http://dx.doi.org/10.1016/j.jcmgh.2021.05.021}, DOI={10.1016/j.jcmgh.2021.05.021}, abstractNote={The transcription factor GATA4 is broadly expressed in nascent foregut endoderm. As development progresses, GATA4 is lost in the domain giving rise to the stratified squamous epithelium of the esophagus and forestomach (FS), while it is maintained in the domain giving rise to the simple columnar epithelium of the hindstomach (HS). Differential GATA4 expression within these domains coincides with the onset of distinct tissue morphogenetic events, suggesting a role for GATA4 in diversifying foregut endoderm into discrete esophageal/FS and HS epithelial tissues. The goal of this study was to determine how GATA4 regulates differential morphogenesis of the mouse gastric epithelium.We used a Gata4 conditional knockout mouse line to eliminate GATA4 in the developing HS and a Gata4 conditional knock-in mouse line to express GATA4 in the developing FS.We found that GATA4-deficient HS epithelium adopted a FS-like fate, and conversely, that GATA4-expressing FS epithelium adopted a HS-like fate. Underlying structural changes in these epithelia were broad changes in gene expression networks attributable to GATA4 directly activating or repressing expression of HS or FS defining transcripts. Our study implicates GATA4 as having a primary role in suppressing an esophageal/FS transcription factor network during HS development to promote columnar epithelium. Moreover, GATA4-dependent phenotypes in developmental mutants reflected changes in gene expression associated with Barrett's esophagus.This study demonstrates that GATA4 is necessary and sufficient to activate the development of simple columnar epithelium, rather than stratified squamous epithelium, in the embryonic stomach. Moreover, similarities between mutants and Barrett's esophagus suggest that developmental biology can provide insight into human disease mechanisms.}, number={4}, journal={Cellular and Molecular Gastroenterology and Hepatology}, publisher={Elsevier BV}, author={DeLaForest, Ann and Kohlnhofer, Bridget M. and Franklin, Olivia D. and Stavniichuk, Roman and Thompson, Cayla A. and Pulakanti, Kirthi and Rao, Sridhar and Battle, Michele A.}, year={2021}, pages={1391–1413} }
 @article{stavniichuk_delaforest_thompson_miller_souza_battle_2021, title={GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells}, volume={11}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/s41598-021-82557-x}, DOI={10.1038/s41598-021-82557-x}, abstractNote={Abstract GATA4 promotes columnar epithelial cell fate during gastric development. When ectopically expressed in the developing mouse forestomach, the tissue emerges as columnar-like rather than stratified squamous with gene expression changes that parallel those observed in the pre-malignant squamous to columnar metaplasia known as Barrett’s esophagus (BE). GATA4 mRNA up-regulation and gene amplification occur in BE and its associated cancer, esophageal adenocarcinoma (EAC), and GATA4 gene amplification correlates with poor patient outcomes. Here, we explored the effect of ectopic expression of GATA4 in mature human esophageal squamous epithelial cells. We found that GATA4 expression in esophageal squamous epithelial cells compromised squamous cell marker gene expression and up-regulated expression of the canonical columnar cell cytokeratin KRT8 . We observed GATA4 occupancy in the p63 , KRT5 , and KRT15 promoters, suggesting that GATA4 directly represses expression of squamous epithelial cell marker genes. Finally, we verified GATA4 protein expression in BE and EAC and found that exposure of esophageal squamous epithelial cells to acid and bile, known BE risk factors, induced GATA4 mRNA expression. We conclude that GATA4 suppresses expression of genes marking the stratified squamous epithelial cell lineage and that this repressive action by GATA4 may have implications in BE and EAC.}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Stavniichuk, Roman and DeLaForest, Ann and Thompson, Cayla A. and Miller, James and Souza, Rhonda F. and Battle, Michele A.}, year={2021}, month={Feb} }
 @article{delaforest_quryshi_frolkis_franklin_battle_2020, title={GATA4 Is Required for Budding Morphogenesis of Posterior Foregut Endoderm in a Model of Human Stomach Development}, volume={7}, ISSN={2296-858X}, url={http://dx.doi.org/10.3389/fmed.2020.00044}, DOI={10.3389/fmed.2020.00044}, abstractNote={Three-dimensional gastrointestinal organoid culture systems provide innovative and tractable models to investigate fundamental developmental biology questions using human cells. The goal of this study was to explore the role of the zinc-finger containing transcription factor GATA4 in gastric development using an organoid-based model of human stomach development. Given GATA4's vital role in the developing mouse gastrointestinal tract, we hypothesized that GATA4 plays an essential role in human stomach development. We generated a human induced pluripotent stem cell (hiPSC) line stably expressing an shRNA targeted against GATA4 (G4KD-hiPSCs) and used an established protocol for the directed differentiation of hiPSCs into stomach organoids. This in vitro model system, informed by studies in multiple non-human model systems, recapitulates the fundamental processes of stomach development, including foregut endoderm patterning, specification, and subsequent tissue morphogenesis and growth, to produce three-dimensional fundic or antral organoids containing functional gastric epithelial cell types. We confirmed that GATA4 depletion did not disrupt hiPSC differentiation to definitive endoderm (DE). However, when G4KD-hiPSC-derived DE cells were directed to differentiate toward budding SOX2+, HNF1B+ posterior foregut spheroids, we observed a striking decrease in the emergence of cell aggregates, with little to no spheroid formation and budding by GATA4-depleted hiPSCs. In contrast, control hiPSC-derived DE cells, expressing GATA4, formed aggregates and budded into spheroids as expected. These data support an essential role for GATA4 during the earliest stages of human stomach development.}, journal={Frontiers in Medicine}, publisher={Frontiers Media SA}, author={DeLaForest, Ann and Quryshi, Afiya F. and Frolkis, Talia S. and Franklin, Olivia D. and Battle, Michele A.}, year={2020}, month={Feb} }
 @article{mccormick_samuels_battle_frolkis_blumin_bock_wells_yan_altman_johnston_2020, title={H+/K+ATPase Expression in the Larynx of Laryngopharyngeal Reflux and Laryngeal Cancer Patients}, volume={131}, ISSN={0023-852X 1531-4995}, url={http://dx.doi.org/10.1002/lary.28643}, DOI={10.1002/lary.28643}, abstractNote={Objectives The gastric H+/K+ ATPase proton pump has previously been shown to be expressed in the human larynx, however its contribution to laryngopharyngeal reflux (LPR) signs, symptoms and associated diseases such as laryngeal cancer is unknown. Proton pump expression in the larynx of patients with LPR and laryngeal cancer was investigated herein. A human hypopharyngeal cell line expressing the proton pump was generated to investigate its effects. Study Design In‐vitro translational. Methods Laryngeal biopsies were obtained from three LPR and eight LSCC patients. ATP4A , ATP4B and HRPT1 were assayed via qPCR. Human hypopharyngeal FaDu cell lines stably expressing proton pump were created using lentiviral transduction and examined via transmission electron microscopy and qPCR for genes associated with inflammation or laryngeal cancer. Results Expression of ATP4A and ATP4B was detected in 3/3 LPR, 4/8 LSCC‐tumor and 3/8 LSCC‐adjacent specimens. Expression of ATP4A and ATP4B in FaDu elicited mitochondrial damage and expression of IL1B , PTGS2 , and TNFA ( P < .0001); expression of ATP4B alone did not. Conclusions Gastric proton pump subunits are expressed in the larynx of LPR and LSCC patients. Mitochondrial damage and changes in gene expression observed in cells expressing the full proton pump, absent in those expressing a single subunit, suggest that acid secretion by functional proton pumps expressed in upper airway mucosa may elicit local cell and molecular changes associated with inflammation and cancer. Level of Evidence NA Laryngoscope , 131:130–135, 2021}, number={1}, journal={The Laryngoscope}, publisher={Wiley}, author={McCormick, Caroline A. and Samuels, Tina L. and Battle, Michele A. and Frolkis, Talia and Blumin, Joel H. and Bock, Jonathan M. and Wells, Clive and Yan, Ke and Altman, Kenneth W. and Johnston, Nikki}, year={2020}, month={Apr}, pages={130–135} }
 @article{fields_delaforest_zogg_may_hagen_komnick_wieser_lundberg_weiler_battle_et al._2019, title={The Adult Murine Intestine is Dependent on Constitutive Laminin-γ1 Synthesis}, volume={9}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/s41598-019-55844-x}, DOI={10.1038/s41598-019-55844-x}, abstractNote={Abstract Laminin-γ1 is required for early embryonic development; however, the need for laminin-γ1 synthesis in adulthood is unknown. A global and inducible mouse model of laminin-γ1 deficiency was generated to address this question. Genetic ablation of the Lamc1 gene in adult mice was rapidly lethal. Despite global Lamc1 gene deletion in tamoxifen-induced mutant mice, there was minimal change in total cardiac, pulmonary, hepatic or renal laminin protein. In contrast, laminin-γ1 was significantly depleted in the small intestines, which showed crypt hyperplasia and dissociation of villous epithelium from adjacent mesenchyme. We conclude that the physiologic requirement for laminin-γ1 synthesis in adult mice is dependent on a tissue-specific basal rate of laminin-γ1 turnover that results in rapid depletion of laminin-γ1 in the intestine.}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Fields, British and DeLaForest, Ann and Zogg, Mark and May, Jennifer and Hagen, Catherine and Komnick, Kristin and Wieser, Jon and Lundberg, Alexander and Weiler, Hartmut and Battle, Michele A. and et al.}, year={2019}, month={Dec} }
 @article{thompson_delaforest_battle_2018, title={Patterning the gastrointestinal epithelium to confer regional-specific functions}, volume={435}, ISSN={0012-1606}, url={http://dx.doi.org/10.1016/j.ydbio.2018.01.006}, DOI={10.1016/j.ydbio.2018.01.006}, number={2}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Thompson, Cayla A. and DeLaForest, Ann and Battle, Michele A.}, year={2018}, month={Mar}, pages={97–108} }
 @article{mitzelfelt_mcdermott-roe_grzybowski_marquez_kuo_riedel_lai_choi_kolander_helbling_et al._2017, title={Efficient Precision Genome Editing in iPSCs via Genetic Co-targeting with Selection}, volume={8}, ISSN={2213-6711}, url={http://dx.doi.org/10.1016/j.stemcr.2017.01.021}, DOI={10.1016/j.stemcr.2017.01.021}, abstractNote={Genome editing in induced pluripotent stem cells is currently hampered by the laborious and expensive nature of identifying homology-directed repair (HDR)-modified cells. We present an approach where isolation of cells bearing a selectable, HDR-mediated editing event at one locus enriches for HDR-mediated edits at additional loci. This strategy, called co-targeting with selection, improves the probability of isolating cells bearing HDR-mediated variants and accelerates the production of disease models.}, number={3}, journal={Stem Cell Reports}, publisher={Elsevier BV}, author={Mitzelfelt, Katie A. and McDermott-Roe, Chris and Grzybowski, Michael N. and Marquez, Maribel and Kuo, Chieh-Ti and Riedel, Michael and Lai, Shuping and Choi, Melinda J. and Kolander, Kurt D. and Helbling, Daniel and et al.}, year={2017}, month={Mar}, pages={491–499} }
 @article{thompson_wojta_pulakanti_rao_dawson_battle_2017, title={GATA4 Is Sufficient to Establish Jejunal Versus Ileal Identity in the Small Intestine}, volume={3}, ISSN={2352-345X}, url={http://dx.doi.org/10.1016/j.jcmgh.2016.12.009}, DOI={10.1016/j.jcmgh.2016.12.009}, abstractNote={Patterning of the small intestinal epithelium along its cephalocaudal axis establishes three functionally distinct regions: duodenum, jejunum, and ileum. Efficient nutrient assimilation and growth depend on the proper spatial patterning of specialized digestive and absorptive functions performed by duodenal, jejunal, and ileal enterocytes. When enterocyte function is disrupted by disease or injury, intestinal failure can occur. One approach to alleviate intestinal failure would be to restore lost enterocyte functions. The molecular mechanisms determining regionally defined enterocyte functions, however, are poorly delineated. We previously showed that GATA binding protein 4 (GATA4) is essential to define jejunal enterocytes. The goal of this study was to test the hypothesis that GATA4 is sufficient to confer jejunal identity within the intestinal epithelium.}, number={3}, journal={Cellular and Molecular Gastroenterology and Hepatology}, publisher={Elsevier BV}, author={Thompson, Cayla A. and Wojta, Kevin and Pulakanti, Kirthi and Rao, Sridhar and Dawson, Paul and Battle, Michele A.}, year={2017}, month={May}, pages={422–446} }
 @article{chin_tsai_finkbeiner_nagy_walker_ethen_williams_battle_spence_2016, title={A Dynamic WNT/β-CATENIN Signaling Environment Leads to WNT-Independent and WNT-Dependent Proliferation of Embryonic Intestinal Progenitor Cells}, volume={7}, ISSN={2213-6711}, url={http://dx.doi.org/10.1016/j.stemcr.2016.09.004}, DOI={10.1016/j.stemcr.2016.09.004}, number={5}, journal={Stem Cell Reports}, publisher={Elsevier BV}, author={Chin, Alana M. and Tsai, Yu-Hwai and Finkbeiner, Stacy R. and Nagy, Melinda S. and Walker, Emily M. and Ethen, Nicole J. and Williams, Bart O. and Battle, Michele A. and Spence, Jason R.}, year={2016}, month={Nov}, pages={826–839} }
 @article{kohlnhofer_thompson_walker_battle_2016, title={GATA4 Regulates Epithelial Cell Proliferation to Control Intestinal Growth and Development in Mice}, volume={2}, ISSN={2352-345X}, url={http://dx.doi.org/10.1016/j.jcmgh.2015.11.010}, DOI={10.1016/j.jcmgh.2015.11.010}, abstractNote={Background & AimsThe embryonic small intestinal epithelium is highly proliferative, and although much is known about mechanisms regulating proliferation in the adult intestine, the mechanisms controlling epithelial cell proliferation in the developing intestine are less clear. GATA4, a transcription factor that regulates proliferation in other developing tissues, is first expressed early in the developing gut in midgut endoderm. GATA4 function within midgut endoderm and the early intestinal epithelium is unknown.MethodsBy using Sonic Hedgehog Cre to eliminate GATA4 in the midgut endoderm of mouse embryos, we determined the impact of loss of GATA4 on intestinal development, including epithelial cell proliferation, between embryonic day (E)9.5 and E18.5.ResultsWe found that intestinal length and width were decreased in GATA4 mutants compared with controls. GATA4-deficient intestinal epithelium contained fewer cells, and epithelial girth was decreased. We further observed a decreased proportion of proliferating epithelial cells at E10.5 and E11.5 in GATA4 mutants. We showed that GATA4 binds to chromatin containing GATA4 consensus binding sites within cyclin D2 (Ccnd2), cyclin-dependent kinase 6 (Cdk6), and frizzled 5 (Fzd5). Moreover, Ccnd2, Cdk6, and Fzd5 transcripts were reduced at E11.5 in GATA4 mutant tissue. Villus morphogenesis was delayed, and villus structure was abnormal in GATA4 mutant intestine.ConclusionsOur data identify GATA4 as an essential regulator of early intestinal epithelial cell proliferation. We propose that GATA4 controls proliferation in part by directly regulating transcription of cell-cycle mediators. Our data further suggest that GATA4 affects proliferation through transcriptional regulation of Fzd5, perhaps by influencing the response of the epithelium to WNT signaling. The embryonic small intestinal epithelium is highly proliferative, and although much is known about mechanisms regulating proliferation in the adult intestine, the mechanisms controlling epithelial cell proliferation in the developing intestine are less clear. GATA4, a transcription factor that regulates proliferation in other developing tissues, is first expressed early in the developing gut in midgut endoderm. GATA4 function within midgut endoderm and the early intestinal epithelium is unknown. By using Sonic Hedgehog Cre to eliminate GATA4 in the midgut endoderm of mouse embryos, we determined the impact of loss of GATA4 on intestinal development, including epithelial cell proliferation, between embryonic day (E)9.5 and E18.5. We found that intestinal length and width were decreased in GATA4 mutants compared with controls. GATA4-deficient intestinal epithelium contained fewer cells, and epithelial girth was decreased. We further observed a decreased proportion of proliferating epithelial cells at E10.5 and E11.5 in GATA4 mutants. We showed that GATA4 binds to chromatin containing GATA4 consensus binding sites within cyclin D2 (Ccnd2), cyclin-dependent kinase 6 (Cdk6), and frizzled 5 (Fzd5). Moreover, Ccnd2, Cdk6, and Fzd5 transcripts were reduced at E11.5 in GATA4 mutant tissue. Villus morphogenesis was delayed, and villus structure was abnormal in GATA4 mutant intestine. Our data identify GATA4 as an essential regulator of early intestinal epithelial cell proliferation. We propose that GATA4 controls proliferation in part by directly regulating transcription of cell-cycle mediators. Our data further suggest that GATA4 affects proliferation through transcriptional regulation of Fzd5, perhaps by influencing the response of the epithelium to WNT signaling.}, number={2}, journal={Cellular and Molecular Gastroenterology and Hepatology}, publisher={Elsevier BV}, author={Kohlnhofer, Bridget M. and Thompson, Cayla A. and Walker, Emily M. and Battle, Michele A.}, year={2016}, month={Mar}, pages={189–209} }
 @article{moore_jin_lo_jung_wang_battle_wollheim_urano_mills_2016, title={Transcriptional Regulation of X-Box-binding Protein One (XBP1) by Hepatocyte Nuclear Factor 4α (HNF4Α) Is Vital to Beta-cell Function}, volume={291}, ISSN={0021-9258}, url={http://dx.doi.org/10.1074/jbc.M115.685750}, DOI={10.1074/jbc.M115.685750}, number={12}, journal={Journal of Biological Chemistry}, publisher={Elsevier BV}, author={Moore, Benjamin D. and Jin, Ramon U. and Lo, Heiyong and Jung, Min and Wang, Haiyan and Battle, Michele A. and Wollheim, Claes B. and Urano, Fumihiko and Mills, Jason C.}, year={2016}, month={Mar}, pages={6146–6157} }
 @article{zhong_brown_kramer_kaleka_petersen_krueger_florence_muelbl_battle_murphy_et al._2015, title={Increased Prefrontal Cortex Neurogranin Enhances Plasticity and Extinction Learning}, volume={35}, ISSN={0270-6474 1529-2401}, url={http://dx.doi.org/10.1523/JNEUROSCI.0274-15.2015}, DOI={10.1523/JNEUROSCI.0274-15.2015}, abstractNote={Increasing plasticity in neurons of the prefrontal cortex (PFC) has been proposed as a possible therapeutic tool to enhance extinction, a process that is impaired in post-traumatic stress disorder, schizophrenia, and addiction. To test this hypothesis, we generated transgenic mice that overexpress neurogranin (a calmodulin-binding protein that facilitates long-term potentiation) in the PFC. Neurogranin overexpression in the PFC enhanced long-term potentiation and increased the rates of extinction learning of both fear conditioning and sucrose self-administration. Our results indicate that elevated neurogranin function within the PFC can enhance local plasticity and increase the rate of extinction learning across different behavioral tasks. Thus, neurogranin can provide a molecular link between enhanced plasticity and enhanced extinction.}, number={19}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Zhong, Ling and Brown, Joshua and Kramer, Audra and Kaleka, Kanwardeep and Petersen, Amber and Krueger, Jamie N. and Florence, Matthew and Muelbl, Matthew J. and Battle, Michelle and Murphy, Geoffrey G. and et al.}, year={2015}, month={May}, pages={7503–7508} }
 @inbook{thompson_battle_2014, place={Hoboken, NJ}, title={Basic Science of Small Intestinal Development}, booktitle={Translational Gastroenterology: Organogenesis to Disease}, publisher={Wiley Blackwell Publishers}, author={Thompson, C.A. and Battle, M.A.}, editor={Gumucio, D.L. and Samuelson, L.C. and Spence, J.R.Editors}, year={2014}, pages={85–97} }
 @article{walker_thompson_kohlnhofer_faber_battle_2014, title={Characterization of the developing small intestine in the absence of either GATA4 or GATA6}, volume={7}, ISSN={1756-0500}, url={http://dx.doi.org/10.1186/1756-0500-7-902}, DOI={10.1186/1756-0500-7-902}, abstractNote={Studies of adult mice lacking either GATA4 or GATA6 in the small intestine demonstrate roles for these factors in small intestinal biology. Deletion of Gata4 in the adult mouse intestine revealed an essential role for GATA4 in jejunal function. Deletion of Gata6 in the adult mouse ileum alters epithelial cell types and ileal enterocyte gene expression. The effect of deletion of Gata4 or Gata6 alone during embryonic small intestinal development, however, has not been examined. We recently demonstrated that loss of both factors in double conditional knockout embryos causes severe defects in jejunal development. Therefore, the goal of this study is to provide phenotypic analysis of the small intestine of single Gata4 and Gata6 conditional knockout embryos. Villin-Cre was used to delete Gata4 or Gata6 in the developing intestinal epithelium. Elimination of either GATA4 or GATA6 in the jejunum, where these factors are co-expressed, caused changes in enterocyte and enteroendocrine cell gene expression. Ectopic expression of markers of the ileal-specific bile acid metabolism pathway was induced in GATA4-deficient jejunum but not in GATA6-deficient jejunum. A subtle increase in goblet cells was also identified in jejunum of both mutants. In GATA6-deficient embryonic ileum, villus length was altered, and enterocyte gene expression was perturbed including ectopic expression of the colon marker Car1. Goblet cells were increased, and enteroendocrine cells were decreased. Overall, we show that aspects of the phenotypes observed in the small intestine of adult Gata4 and Gata6 conditional knockout mice emerge during development. The effect of eliminating GATA6 from the developing ileum was greater than that of eliminating either GATA4 or GATA6 from the developing jejunum likely reflecting functional redundancy between these factors in the jejunum. Although GATA4 and GATA6 functions overlap, our data also suggest unique functions for GATA4 and GATA6 within the developing intestine. GATA4 likely operates independently of GATA6 within the jejunum to regulate jejunal versus ileal enterocyte identity and consequently jejunal physiology. GATA6 likely regulates enteroendocrine cell differentiation cell autonomously whereas GATA4 affects this population indirectly.}, number={1}, journal={BMC Research Notes}, publisher={Springer Science and Business Media LLC}, author={Walker, Emily M and Thompson, Cayla A and Kohlnhofer, Bridget M and Faber, Mary L and Battle, Michele A}, year={2014}, month={Dec} }
 @article{walker_thompson_battle_2014, title={GATA4 and GATA6 regulate intestinal epithelial cytodifferentiation during development}, volume={392}, ISSN={0012-1606}, url={http://dx.doi.org/10.1016/j.ydbio.2014.05.017}, DOI={10.1016/j.ydbio.2014.05.017}, number={2}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Walker, Emily M. and Thompson, Cayla A. and Battle, Michele A.}, year={2014}, month={Aug}, pages={283–294} }
 @inbook{thompson_battle_2014, place={Hoboken, NJ}, title={Translational Gastroenterology}, booktitle={Basic Science of Small Intestinal Development}, publisher={Wiley Blackwell Publishers}, author={Thompson, C.A. and Battle, M.A.}, editor={Gumucio, D.L. and Samuelson, L.C. and Spence, J.R.Editors}, year={2014}, pages={85–97} }
 @article{bondow_faber_wojta_walker_battle_2012, title={E-cadherin is required for intestinal morphogenesis in the mouse}, volume={371}, ISSN={0012-1606}, url={http://dx.doi.org/10.1016/j.ydbio.2012.06.005}, DOI={10.1016/j.ydbio.2012.06.005}, number={1}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Bondow, Benjamin J. and Faber, Mary L. and Wojta, Kevin J. and Walker, Emily M. and Battle, Michele A.}, year={2012}, month={Nov}, pages={1–12} }
 @article{patankar_obrowsky_doddapattar_hoefler_battle_levak-frank_kratky_2012, title={Intestinal GATA4 deficiency protects from diet-induced hepatic steatosis}, volume={57}, ISSN={0168-8278}, url={http://dx.doi.org/10.1016/j.jhep.2012.06.028}, DOI={10.1016/j.jhep.2012.06.028}, abstractNote={GATA4, a zinc finger domain transcription factor, is critical for jejunal identity. Mice with an intestine-specific GATA4 deficiency (GATA4iKO) are resistant to diet-induced obesity and insulin resistance. Although they have decreased intestinal lipid absorption, hepatic de novo lipogenesis is inhibited. Here, we investigated dietary lipid-dependent and independent effects on the development of steatosis and fibrosis in GATA4iKO mice.GATA4iKO and control mice were fed a Western-type diet (WTD) or a methionine and choline-deficient diet (MCDD) for 20 and 3 weeks, respectively. Functional effects of GATA4iKO on diet-induced liver steatosis were investigated.WTD-but not MCDD-fed GATA4iKO mice showed lower hepatic concentrations of triglycerides, free fatty acids, and thiobarbituric acid reactive species and had reduced expression of lipogenic as well as fibrotic genes compared with controls. Reduced nuclear sterol regulatory element-binding protein-1c protein levels were accompanied by lower lipogenic gene expression. Oil red O and Sirius Red staining of liver sections confirmed the observed reduction in hepatic lipid accumulation and fibrosis. Immunohistochemical staining revealed an increased number of jejunal glucagon-like peptide 1 (GLP-1) positive cells in GATA4iKO mice. Consequently, we found enhanced phosphorylation of hepatic AMP-activated protein kinase and acetyl-CoA carboxylase alpha.Our results provide strong indications for a protective effect of intestinal GATA4 deficiency on the development of hepatic steatosis and fibrosis via GLP-1, thereby blocking hepatic de novo lipogenesis.}, number={5}, journal={Journal of Hepatology}, publisher={Elsevier BV}, author={Patankar, Jay V. and Obrowsky, Sascha and Doddapattar, Prakash and Hoefler, Gerald and Battle, Michele and Levak-Frank, Sanja and Kratky, Dagmar}, year={2012}, month={Nov}, pages={1061–1068} }
 @article{xuan_borok_decker_battle_duncan_hale_macdonald_sussel_2012, title={Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis}, volume={122}, ISSN={0021-9738}, url={http://dx.doi.org/10.1172/JCI63352}, DOI={10.1172/JCI63352}, abstractNote={Pancreatic agenesis is a human disorder caused by defects in pancreas development. To date, only a few genes have been linked to pancreatic agenesis in humans, with mutations in pancreatic and duodenal homeobox 1 (PDX1) and pancreas-specific transcription factor 1a (PTF1A) reported in only 5 families with described cases. Recently, mutations in GATA6 have been identified in a large percentage of human cases, and a GATA4 mutant allele has been implicated in a single case. In the mouse, Gata4 and Gata6 are expressed in several endoderm-derived tissues, including the pancreas. To analyze the functions of GATA4 and/or GATA6 during mouse pancreatic development, we generated pancreas-specific deletions of Gata4 and Gata6. Surprisingly, loss of either Gata4 or Gata6 in the pancreas resulted in only mild pancreatic defects, which resolved postnatally. However, simultaneous deletion of both Gata4 and Gata6 in the pancreas caused severe pancreatic agenesis due to disruption of pancreatic progenitor cell proliferation, defects in branching morphogenesis, and a subsequent failure to induce the differentiation of progenitor cells expressing carboxypeptidase A1 (CPA1) and neurogenin 3 (NEUROG3). These studies address the conserved and nonconserved mechanisms underlying GATA4 and GATA6 function during pancreas development and provide a new mouse model to characterize the underlying developmental defects associated with pancreatic agenesis.}, number={10}, journal={Journal of Clinical Investigation}, publisher={American Society for Clinical Investigation}, author={Xuan, Shouhong and Borok, Matthew J. and Decker, Kimberly J. and Battle, Michele A. and Duncan, Stephen A. and Hale, Michael A. and Macdonald, Raymond J. and Sussel, Lori}, year={2012}, month={Oct}, pages={3516–3528} }
 @article{shulzhenko_morgun_hsiao_battle_yao_gavrilova_orandle_mayer_macpherson_mccoy_et al._2011, title={Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut}, volume={17}, ISSN={1078-8956 1546-170X}, url={http://dx.doi.org/10.1038/nm.2505}, DOI={10.1038/nm.2505}, number={12}, journal={Nature Medicine}, publisher={Springer Science and Business Media LLC}, author={Shulzhenko, Natalia and Morgun, Andrey and Hsiao, William and Battle, Michele and Yao, Michael and Gavrilova, Oksana and Orandle, Marlene and Mayer, Lloyd and Macpherson, Andrew J and McCoy, Kathy D and et al.}, year={2011}, month={Nov}, pages={1585–1593} }
 @article{delaforest_nagaoka_si-tayeb_noto_konopka_battle_duncan_2011, title={HNF4A is essential for specification of hepatic progenitors from human pluripotent stem cells}, volume={138}, ISSN={1477-9129 0950-1991}, url={http://dx.doi.org/10.1242/dev.062547}, DOI={10.1242/dev.062547}, abstractNote={The availability of pluripotent stem cells offers the possibility of using such cells to model hepatic disease and development. With this in mind, we previously established a protocol that facilitates the differentiation of both human embryonic stem cells and induced pluripotent stem cells into cells that share many characteristics with hepatocytes. The use of highly defined culture conditions and the avoidance of feeder cells or embryoid bodies allowed synchronous and reproducible differentiation to occur. The differentiation towards a hepatocyte-like fate appeared to recapitulate many of the developmental stages normally associated with the formation of hepatocytes in vivo. In the current study, we addressed the feasibility of using human pluripotent stem cells to probe the molecular mechanisms underlying human hepatocyte differentiation. We demonstrate (1) that human embryonic stem cells express a number of mRNAs that characterize each stage in the differentiation process, (2) that gene expression can be efficiently depleted throughout the differentiation time course using shRNAs expressed from lentiviruses and (3) that the nuclear hormone receptor HNF4A is essential for specification of human hepatic progenitor cells by establishing the expression of the network of transcription factors that controls the onset of hepatocyte cell fate.}, number={19}, journal={Development}, publisher={The Company of Biologists}, author={DeLaForest, Ann and Nagaoka, Masato and Si-Tayeb, Karim and Noto, Fallon K. and Konopka, Genevieve and Battle, Michele A. and Duncan, Stephen A.}, year={2011}, month={Oct}, pages={4143–4153} }
 @article{patankar_chandak_obrowsky_pfeifer_diwoky_uellen_sattler_stollberger_hoefler_heinemann_et al._2011, title={Loss of intestinal GATA4 prevents diet-induced obesity and promotes insulin sensitivity in mice}, volume={300}, ISSN={0193-1849 1522-1555}, url={http://dx.doi.org/10.1152/ajpendo.00457.2010}, DOI={10.1152/ajpendo.00457.2010}, abstractNote={Transcriptional regulation of small intestinal gene expression controls plasma total cholesterol (TC) and triglyceride (TG) levels, which are major determinants of metabolic diseases. GATA4, a zinc finger domain transcription factor, is critical for jejunal identity, and intestinal GATA4 deficiency leads to a jejunoileal transition. Although intestinal GATA4 ablation is known to misregulate jejunal gene expression, its pathophysiological impact on various components of metabolic syndrome remains unknown. Here, we used intestine-specific GATA4 knockout (GATA4iKO) mice to dissect the contribution of GATA4 on obesity development. We challenged adult GATA4iKO mice and control littermates with a Western-type diet (WTD) for 20 wk. Our findings show that WTD-fed GATA4iKO mice are resistant to diet-induced obesity. Accordingly, plasma TG and TC levels are markedly decreased. Intestinal lipid absorption in GATA4iKO mice was strongly reduced, whereas luminal lipolysis was unaffected. GATA4iKO mice displayed a greater glucagon-like peptide-1 (GLP-1) release on normal chow and even after long-term challenge with WTD remained glucose sensitive. In summary, our findings show that the absence of intestinal GATA4 has a beneficial effect on decreasing intestinal lipid absorption causing resistance to hyperlipidemia and obesity. In addition, we show that increased GLP-1 release in GATA4iKO mice decreases the risk for development of insulin resistance.}, number={3}, journal={American Journal of Physiology-Endocrinology and Metabolism}, publisher={American Physiological Society}, author={Patankar, Jay V. and Chandak, Prakash G. and Obrowsky, Sascha and Pfeifer, Thomas and Diwoky, Clemens and Uellen, Andreas and Sattler, Wolfgang and Stollberger, Rudolf and Hoefler, Gerald and Heinemann, Akos and et al.}, year={2011}, month={Mar}, pages={E478–E488} }
 @article{si-tayeb_noto_nagaoka_li_battle_duris_north_dalton_duncan_2010, title={Highly Efficient Generation of Human Hepatocyte–Like Cells From Induced Pluripotent Stem Cells}, volume={51}, ISSN={0270-9139}, url={http://dx.doi.org/10.1002/hep.23354}, DOI={10.1002/hep.23354}, abstractNote={There exists a worldwide shortage of donor livers available for orthotropic liver transplantation and hepatocyte transplantation therapies. In addition to their therapeutic potential, primary human hepatocytes facilitate the study of molecular and genetic aspects of human hepatic disease and development and provide a platform for drug toxicity screens and identification of novel pharmaceuticals with potential to treat a wide array of metabolic diseases. The demand for human hepatocytes, therefore, heavily outweighs their availability. As an alternative to using donor livers as a source of primary hepatocytes, we explored the possibility of generating patient-specific human hepatocytes from induced pluripotent stem (iPS) cells. Conclusion: We demonstrate that mouse iPS cells retain full potential for fetal liver development and describe a procedure that facilitates the efficient generation of highly differentiated human hepatocyte-like cells from iPS cells that display key liver functions and can integrate into the hepatic parenchyma in vivo . (Hepatology 2010.)}, number={1}, journal={Hepatology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Si-Tayeb, Karim and Noto, Fallon K. and Nagaoka, Masato and Li, Jixuan and Battle, Michele A. and Duris, Christine and North, Paula E. and Dalton, Stephen and Duncan, Stephen A.}, year={2010}, month={Jan}, pages={297–305} }
 @article{chamouton_hansmannel_bonzo_clémencet_chevillard_battle_martin_pineau_duncan_gonzalez_et al._2010, title={The Peroxisomal<i>3-keto-acyl-CoA thiolase B</i>Gene Expression Is under the Dual Control of PPARα and HNF4α in the Liver}, volume={2010}, ISSN={1687-4757 1687-4765}, url={http://dx.doi.org/10.1155/2010/352957}, DOI={10.1155/2010/352957}, abstractNote={PPARα and HNF4α are nuclear receptors that control gene transcription by direct binding to specific nucleotide sequences. Using transgenic mice deficient for either PPARα or HNF4α, we show that the expression of the peroxisomal 3-keto-acyl-CoA thiolase B (Thb) is under the dependence of these two transcription factors. Transactivation and gel shift experiments identified a novel PPAR response element within intron 3 of the Thb gene, by which PPARα but not HNF4α transactivates. Intriguingly, we found that HNF4α enhanced PPARα/RXRα transactivation from TB PPRE3 in a DNA-binding independent manner. Coimmunoprecipitation assays supported the hypothesis that HNF4α was physically interacting with RXRα. RT-PCR performed with RNA from liver-specific HNF4α-null mice confirmed the involvement of HNF4α in the PPARα-regulated induction of Thb by Wy14,643. Overall, we conclude that HNF4α enhances the PPARα-mediated activation of Thb gene expression in part through interaction with the obligate PPARα partner, RXRα.}, journal={PPAR Research}, publisher={Hindawi Limited}, author={Chamouton, J. and Hansmannel, F. and Bonzo, J. A. and Clémencet, M. C. and Chevillard, G. and Battle, M. and Martin, P. and Pineau, T. and Duncan, S. and Gonzalez, F. J. and et al.}, year={2010}, pages={1–17} }
 @article{sun_battle_misra_duncan_2009, title={Hepatocyte expression of serum response factor is essential for liver function, hepatocyte proliferation and survival, and postnatal body growth in mice #}, volume={49}, ISSN={0270-9139}, url={http://dx.doi.org/10.1002/hep.22834}, DOI={10.1002/hep.22834}, abstractNote={Serum response factor (SRF) is a transcription factor that binds to a CarG box motif within the serum response element of genes that are expressed in response to mitogens. SRF plays essential roles in muscle and nervous system development; however, little is known about the role of SRF during liver growth and function. To examine the function of SRF in the liver, we generated mice in which the Srf gene was specifically disrupted in hepatocytes. The survival of mice lacking hepatic SRF activity was lower than that of control mice; moreover, surviving mutant mice had lower blood glucose and triglyceride levels compared with control mice. In addition, SrfloxP/loxPAlfpCre mice were smaller and had severely depressed levels of serum insulin-like growth factor 1 (IGF-1). Srf-deficient livers were also smaller than control livers, and liver cell proliferation and viability were compromised. Gene array analysis of SRF depleted livers revealed a reduction in many messenger RNAs, including those encoding components of the growth hormone/IGF-1 pathway, cyclins, several metabolic regulators, and cytochrome p450 enzymes. Conclusion: SRF is essential for hepatocyte proliferation and survival, liver function, and control of postnatal body growth by regulating hepatocyte gene expression. (HEPATOLOGY 2009.)}, number={5}, journal={Hepatology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Sun, Kai and Battle, Michele A. and Misra, Ravi P. and Duncan, Stephen A.}, year={2009}, month={May}, pages={1645–1654} }
 @article{battle_bondow_iverson_adams_jandacek_tso_duncan_2008, title={GATA4 Is Essential for Jejunal Function in Mice}, volume={135}, ISSN={0016-5085}, url={http://dx.doi.org/10.1053/j.gastro.2008.07.074}, DOI={10.1053/j.gastro.2008.07.074}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Battle, Michele A. and Bondow, Benjamin J. and Iverson, Moriah A. and Adams, Scott J. and Jandacek, Ronald J. and Tso, Patrick and Duncan, Stephen A.}, year={2008}, month={Nov}, pages={1676–1686.e1} }
 @article{luebke‐wheeler_zhang_battle_si‐tayeb_garrison_chhinder_li_kaufman_duncan_2008, title={Hepatocyte nuclear factor 4α is implicated in endoplasmic reticulum stress–induced acute phase response by regulating expression of cyclic adenosine monophosphate responsive element binding protein H†}, volume={48}, ISSN={0270-9139}, url={http://dx.doi.org/10.1002/hep.22439}, DOI={10.1002/hep.22439}, abstractNote={Loss of the nuclear hormone receptor hepatocyte nuclear factor 4α (HNF4α) in hepatocytes results in a complex pleiotropic phenotype that includes a block in hepatocyte differentiation and a severe disruption to liver function. Recent analyses have shown that hepatic gene expression is severely affected by the absence of HNF4α, with expression of 567 genes reduced by ≥2.5-fold (P ≤ 0.05) in Hnf4α−/− fetal livers. Although many of these genes are direct targets, HNF4α has also been shown to regulate expression of other liver transcription factors, and this raises the possibility that the dependence on HNF4α for normal expression of some genes may be indirect. We postulated that the identification of transcription factors whose expression is regulated by HNF4α might reveal roles for HNF4α in controlling hepatic functions that were not previously appreciated. Here we identify cyclic adenosine monophosphate responsive element binding protein H (CrebH) as a transcription factor whose messenger RNA can be identified in both the embryonic mouse liver and adult mouse liver and whose expression is dependent on HNF4α. Analyses of genomic DNA revealed an HNF4α binding site upstream of the CrebH coding sequence that was occupied by HNF4α in fetal livers and facilitated transcriptional activation of a reporter gene in transient transfection analyses. Although CrebH is highly expressed during hepatogenesis, CrebH−/− mice were viable and healthy and displayed no overt defects in liver formation. However, upon treatment with tunicamycin, which induces an endoplasmic reticulum (ER)–stress response, CrebH−/− mice displayed reduced expression of acute phase response proteins. Conclusion: These data implicate HNF4α in having a role in controlling the acute phase response of the liver induced by ER stress by regulating expression of CrebH. (HEPATOLOGY 2008.)}, number={4}, journal={Hepatology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Luebke‐Wheeler, Jennifer and Zhang, Kezhong and Battle, Michele and Si‐Tayeb, Karim and Garrison, Wendy and Chhinder, Sodhi and Li, Jixuan and Kaufman, Randal J. and Duncan, Stephen A.}, year={2008}, month={Oct}, pages={1242–1250} }
 @article{zhao_watt_battle_li_bondow_duncan_2008, title={Loss of both GATA4 and GATA6 blocks cardiac myocyte differentiation and results in acardia in mice}, volume={317}, ISSN={0012-1606}, url={http://dx.doi.org/10.1016/j.ydbio.2008.03.013}, DOI={10.1016/j.ydbio.2008.03.013}, number={2}, journal={Developmental Biology}, publisher={Elsevier BV}, author={Zhao, Roong and Watt, Alistair J. and Battle, Michele A. and Li, Jixuan and Bondow, Benjamin J. and Duncan, Stephen A.}, year={2008}, month={May}, pages={614–619} }
 @article{garrison_battle_yang_kaestner_sladek_duncan_2006, title={Hepatocyte Nuclear Factor 4α Is Essential for Embryonic Development of the Mouse Colon}, volume={130}, ISSN={0016-5085}, url={http://dx.doi.org/10.1053/j.gastro.2006.01.003}, DOI={10.1053/j.gastro.2006.01.003}, number={4}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Garrison, Wendy D. and Battle, Michele A. and Yang, Chuhu and Kaestner, Klaus H. and Sladek, Frances M. and Duncan, Stephen A.}, year={2006}, month={Apr}, pages={19.e1–19.e} }
 @article{battle_konopka_parviz_gaggl_yang_sladek_duncan_2006, title={Hepatocyte nuclear factor 4α orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver}, volume={103}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.0600246103}, DOI={10.1073/pnas.0600246103}, abstractNote={Epithelial formation is a central facet of organogenesis that relies on intercellular junction assembly to create functionally distinct apical and basal cell surfaces. How this process is regulated during embryonic development remains obscure. Previous studies using conditional knockout mice have shown that loss of hepatocyte nuclear factor 4alpha (HNF4alpha) blocks the epithelial transformation of the fetal liver, suggesting that HNF4alpha is a central regulator of epithelial morphogenesis. Although HNF4alpha-null hepatocytes do not express E-cadherin (also called CDH1), we show here that E-cadherin is dispensable for liver development, implying that HNF4alpha regulates additional aspects of epithelial formation. Microarray and molecular analyses reveal that HNF4alpha regulates the developmental expression of a myriad of proteins required for cell junction assembly and adhesion. Our findings define a fundamental mechanism through which generation of tissue epithelia during development is coordinated with the onset of organ function.}, number={22}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Battle, Michele A. and Konopka, Genevieve and Parviz, Fereshteh and Gaggl, Alexandra Lerch and Yang, Chuhu and Sladek, Frances M. and Duncan, Stephen A.}, year={2006}, month={May}, pages={8419–8424} }
 @article{rufibach_duncan_battle_deeb_2006, title={Transcriptional regulation of the human hepatic lipase (LIPC) gene promoter}, volume={47}, ISSN={0022-2275}, url={http://dx.doi.org/10.1194/jlr.M600082-JLR200}, DOI={10.1194/jlr.M600082-JLR200}, abstractNote={Hepatic lipase (HL) plays a key role in the metabolism of plasma lipoproteins, and its level of activity requires tight regulation, given the association of both low and high levels with atherosclerosis and coronary artery disease. However, little is known about the factors responsible for HL expression. Here, we report that the human hepatic lipase gene (LIPC) promoter is regulated by hepatocyte nuclear factor 4alpha (HNF4alpha), peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), apolipoprotein A-I regulatory protein-1 (ARP-1), and hepatocyte nuclear factor 1alpha (HNF1alpha). Reporter analysis showed that HNF4alpha directly regulates the LIPC promoter via two newly identified direct repeat elements, DR1 and DR4. PGC-1alpha is capable of stimulating the HNF4alpha-dependent transactivation of the LIPC promoter. ARP-1 displaces HNF4alpha from the DR1 site and blocks its ability to activate the LIPC promoter. Induction by HNF1alpha requires the HNF1 binding site and upon cotransfection with HNF4alpha leads to an additive effect. In addition, the in vivo relevance of HNF4alpha in LIPC expression is shown by the ability of the HNF4alpha antagonist Medica 16 to repress endogenous LIPC mRNA expression. Furthermore, disruption of Hnf4alpha in mice prevents the expression of HL mRNA in liver. The overall effect these transcription factors have on HL expression will ultimately depend on the interplay between these various factors and their relative intracellular concentrations.}, number={7}, journal={Journal of Lipid Research}, publisher={Elsevier BV}, author={Rufibach, Laura E. and Duncan, Stephen A. and Battle, Michele and Deeb, Samir S.}, year={2006}, month={Jul}, pages={1463–1477} }
 @article{watt_battle_li_duncan_2004, title={GATA4 is essential for formation of the proepicardium and regulates cardiogenesis}, volume={101}, ISSN={0027-8424 1091-6490}, url={http://dx.doi.org/10.1073/pnas.0400752101}, DOI={10.1073/pnas.0400752101}, abstractNote={The role of GATA4 during the earliest stages of cardiogenesis has not been defined because Gata4 knockout embryos suffer an early developmental arrest caused by deficiencies in extraembryonic visceral endoderm function. We have used tetraploid embryo complementation to rescue these defects and generated clonal embryonic day 9.5 Gata4(-/-) embryos directly from embryonic stem cells. GATA4-null embryos display heart defects characterized by disrupted looping morphogenesis, septation, and a hypoplastic ventricular myocardium. We find that myocardial gene expression is relatively normal in GATA4-null hearts including expression of GATA6. Moreover, GATA4 expression in the endocardium is dispensable for trabeculae formation. Remarkably, the proepicardium is absent in GATA4-null embryos, blocking formation of the epicardium. Therefore, we propose that the observed myocardial defects may be a secondary consequence of loss of the proepicardium. These findings definitively demonstrate a requirement for GATA4 during early cardiac development and identify an essential factor for generation of the proepicardium.}, number={34}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Watt, Alistair J. and Battle, Michele A. and Li, Jixuan and Duncan, Stephen A.}, year={2004}, month={Aug}, pages={12573–12578} }
 @article{battle_maher_mccormick_2003, title={ST7 Is a Novel Low-Density Lipoprotein Receptor-Related Protein (LRP) with a Cytoplasmic Tail that Interacts with Proteins Related to Signal Transduction Pathways}, volume={42}, ISSN={0006-2960 1520-4995}, url={http://dx.doi.org/10.1021/bi034081y}, DOI={10.1021/bi034081y}, abstractNote={In 1997, McCormick and co-workers identified a novel putative tumor suppressor gene, designated ST7, encoding a unique protein with transmembrane receptor characteristics [Qing et al. (1999) Oncogene 18, 335-342]. Using degenerate primers corresponding to the highly conserved region of the ligand-binding domains of members of the low-density lipoprotein receptor (LDLR) superfamily, Ishii et al. [Genomics (1998) 51, 132-135] discovered a low-density lipoprotein receptor-related protein (LRP) that closely resembles ST7. Later, another LRP closely resembling ST7 and LRP3 was found (murine LRP9) [Sugiyama et al. (2000) Biochemistry 39, 15817-15825]. These results strongly suggested that ST7 was also a novel member of the low-density lipoprotein receptor superfamily. Proteins of this superfamily have been shown to function in endocytosis and/or signal transduction. To evaluate the relationship of ST7 to the LDLR superfamily proteins and to determine whether ST7 may function in endocytosis and/or signal transduction, we used proteomic tools to analyze the functional motifs present in the protein. Our results indicate that ST7 is a member of a subfamily of the LDLR superfamily and that its cytoplasmic domain contains several motifs implicated in endocytosis and signal transduction. Use of the yeast two-hybrid system to identify proteins that associate with ST7's cytoplasmic domain revealed that this domain interacts with three proteins involved in signal transduction and/or endocytosis, viz., receptor for activated protein C kinase 1 (RACK1), muscle integrin binding protein (MIBP), and SMAD anchor for receptor activation (SARA), suggesting that ST7, like other proteins in the LDLR superfamily, functions in these two pathways. Clearly, ST7 is an LRP, and therefore, it should now be referred to as LRP12.}, number={24}, journal={Biochemistry}, publisher={American Chemical Society (ACS)}, author={Battle, Michele A. and Maher, Veronica M. and McCormick, J. Justin}, year={2003}, month={May}, pages={7270–7282} }