@article{brooks_moorman_bhattacharya_prudhomme_land_alcorn_sharma_pe'er_zallen_2024, title={A single-cell atlas of spatial and temporal gene expression in the mouse cranial neural plate}, url={https://doi.org/10.1101/2024.08.25.609458}, DOI={10.1101/2024.08.25.609458}, abstractNote={The formation of the mammalian brain requires regionalization and morphogenesis of the cranial neural plate, which transforms from an epithelial sheet into a closed tube that provides the structural foundation for neural patterning and circuit formation. Sonic hedgehog (SHH) signaling is important for cranial neural plate patterning and closure, but the transcriptional changes that give rise to the spatially regulated cell fates and behaviors that build the cranial neural tube have not been systematically analyzed. Here we used single-cell RNA sequencing to generate an atlas of gene expression at six consecutive stages of cranial neural tube closure in the mouse embryo. Ordering transcriptional profiles relative to the major axes of gene expression predicted spatially regulated expression of 870 genes along the anterior-posterior and mediolateral axes of the cranial neural plate and reproduced known expression patterns with over 85% accuracy. Single-cell RNA sequencing of embryos with activated SHH signaling revealed distinct SHH-regulated transcriptional programs in the developing forebrain, midbrain, and hindbrain, suggesting a complex interplay between anterior-posterior and mediolateral patterning systems. These results define a spatiotemporally resolved map of gene expression during cranial neural tube closure and provide a resource for investigating the transcriptional events that drive early mammalian brain development.}, author={Brooks, Eric R. and Moorman, Andrew R. and Bhattacharya, Bhaswati and Prudhomme, Ian and Land, Max and Alcorn, Heather L. and Sharma, Roshan and Pe'er, Dana and Zallen, Jennifer A.}, year={2024}, month={Aug} }
 @article{brooks_moorman_bhattacharya_prudhomme_land_alcorn_sharma_pe’er_zallen_2024, title={A single-cell atlas of spatial and temporal gene expression in the mouse cranial neural plate}, url={https://doi.org/10.7554/eLife.102819.1}, DOI={10.7554/eLife.102819.1}, author={Brooks, Eric R and Moorman, Andrew R and Bhattacharya, Bhaswati and Prudhomme, Ian and Land, Max and Alcorn, Heather L and Sharma, Roshan and Pe’er, Dana and Zallen, Jennifer A}, year={2024}, month={Nov} }
 @article{brooks_moorman_bhattacharya_prudhomme_land_alcorn_sharma_pe’er_zallen_2024, title={A single-cell atlas of spatial and temporal gene expression in the mouse cranial neural plate}, url={https://doi.org/10.7554/eLife.102819}, DOI={10.7554/eLife.102819}, author={Brooks, Eric R and Moorman, Andrew R and Bhattacharya, Bhaswati and Prudhomme, Ian and Land, Max and Alcorn, Heather L and Sharma, Roshan and Pe’er, Dana and Zallen, Jennifer A}, year={2024}, month={Nov} }
 @article{brooks_islam_anderson_zallen_2020, title={Sonic hedgehog signaling directs patterned cell remodeling during cranial neural tube closure}, volume={10}, url={https://doi.org/10.1101/2020.10.13.337915}, DOI={10.1101/2020.10.13.337915}, abstractNote={AbstractNeural tube closure defects are a major cause of infant mortality, with exencephaly accounting for nearly one-third of cases. However, the mechanisms of cranial neural tube closure are not well understood. Here we show that this process involves a tissue-wide pattern of apical constriction controlled by Sonic hedgehog (Shh) signaling. Midline cells in the mouse midbrain neuroepithelium are short with large apical surfaces, whereas lateral cells are taller and undergo synchronous apical constriction, driving neural fold elevation. Embryos lacking the Shh effector Gli2 fail to produce appropriate midline cell architecture, whereas embryos with expanded Shh signaling, including the IFT-A complex mutantsIft122andTtc21band embryos expressing activated Smoothened, display apical constriction defects in lateral cells. Disruption of lateral, but not midline, cell remodeling results in exencephaly. These results reveal a morphogenetic program of patterned apical constriction governed by Shh signaling that generates structural changes in the developing mammalian brain.}, publisher={Cold Spring Harbor Laboratory}, author={Brooks, Eric R. and Islam, Mohammed T. and Anderson, Kathryn V. and Zallen, Jennifer A.}, year={2020}, month={Oct} }
 @article{brooks_islam_anderson_zallen_2020, title={Sonic hedgehog signaling directs patterned cell remodeling during cranial neural tube closure}, volume={9}, url={https://doi.org/10.7554/eLife.60234}, DOI={10.7554/eLife.60234}, abstractNote={Neural tube closure defects are a major cause of infant mortality, with exencephaly accounting for nearly one-third of cases. However, the mechanisms of cranial neural tube closure are not well understood. Here, we show that this process involves a tissue-wide pattern of apical constriction controlled by Sonic hedgehog (Shh) signaling. Midline cells in the mouse midbrain neuroepithelium are flat with large apical surfaces, whereas lateral cells are taller and undergo synchronous apical constriction, driving neural fold elevation. Embryos lacking the Shh effector Gli2 fail to produce appropriate midline cell architecture, whereas embryos with expanded Shh signaling, including the IFT-A complex mutantsIft122andTtc21band embryos expressing activated Smoothened, display apical constriction defects in lateral cells. Disruption of lateral, but not midline, cell remodeling results in exencephaly. These results reveal a morphogenetic program of patterned apical constriction governed by Shh signaling that generates structural changes in the developing mammalian brain.}, journal={eLife}, publisher={eLife Sciences Publications, Ltd}, author={Brooks, Eric R and Islam, Mohammed Tarek and Anderson, Kathryn V and Zallen, Jennifer A}, year={2020}, month={Oct} }
 @article{in vivo investigation of cilia structure and function using xenopus._2015, url={https://europepmc.org/articles/PMC4433029}, DOI={10.1016/bs.mcb.2015.01.018}, abstractNote={Cilia are key organelles in development and homeostasis. The ever-expanding complement of cilia associated proteins necessitates rapid and tractable models for in vivo functional investigation. Xenopus laevis provides an attractive model for such studies, having multiple ciliated populations, including primary and multiciliated tissues. The rapid external development of Xenopus and the large cells make it an especially excellent platform for imaging studies. Here we present embryological and cell biological methods for the investigation of cilia structure and function in X. laevis, with a focus on quantitative live and fixed imaging.}, journal={Methods in cell biology}, year={2015}, month={Mar} }
 @article{coordinated genomic control of ciliogenesis and cell movement by rfx2._2014, url={https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24424412/?tool=EBI}, DOI={10.7554/elife.01439}, abstractNote={The mechanisms linking systems-level programs of gene expression to discrete cell biological processes in vivo remain poorly understood. In this study, we have defined such a program for multi-ciliated epithelial cells (MCCs), a cell type critical for proper development and homeostasis of the airway, brain and reproductive tracts. Starting from genomic analysis of the cilia-associated transcription factor Rfx2, we used bioinformatics and in vivo cell biological approaches to gain insights into the molecular basis of cilia assembly and function. Moreover, we discovered a previously un-recognized role for an Rfx factor in cell movement, finding that Rfx2 cell-autonomously controls apical surface expansion in nascent MCCs. Thus, Rfx2 coordinates multiple, distinct gene expression programs in MCCs, regulating genes that control cell movement, ciliogenesis, and cilia function. As such, the work serves as a paradigm for understanding genomic control of cell biological processes that span from early cell morphogenetic events to terminally differentiated cellular functions.}, journal={eLife}, year={2014}, month={Jan} }
 @article{multiciliated cells._2014, url={https://europepmc.org/articles/PMC4441396}, DOI={10.1016/j.cub.2014.08.047}, abstractNote={Cilia are microtubule-based projections that serve a wide variety of essential functions in animal cells. Defects in cilia structure or function have recently been found to underlie diverse human diseases. While many eukaryotic cells possess only one or two cilia, some cells, including those of many unicellular organisms, exhibit many cilia. In vertebrates, multiciliated cells are a specialized population of post-mitotic cells decorated with dozens of motile cilia that beat in a polarized and synchronized fashion to drive directed fluid flow across an epithelium. Dysfunction of human multiciliated cells is associated with diseases of the brain, airway and reproductive tracts. Despite their importance, multiciliated cells are relatively poorly studied and we are only beginning to understand the mechanisms underlying their development and function. Here, we review the general phylogeny and physiology of multiciliation and detail our current understanding of the developmental and cellular events underlying the specification, differentiation and function of multiciliated cells in vertebrates. Cilia are microtubule-based projections that serve a wide variety of essential functions in animal cells. Defects in cilia structure or function have recently been found to underlie diverse human diseases. While many eukaryotic cells possess only one or two cilia, some cells, including those of many unicellular organisms, exhibit many cilia. In vertebrates, multiciliated cells are a specialized population of post-mitotic cells decorated with dozens of motile cilia that beat in a polarized and synchronized fashion to drive directed fluid flow across an epithelium. Dysfunction of human multiciliated cells is associated with diseases of the brain, airway and reproductive tracts. Despite their importance, multiciliated cells are relatively poorly studied and we are only beginning to understand the mechanisms underlying their development and function. Here, we review the general phylogeny and physiology of multiciliation and detail our current understanding of the developmental and cellular events underlying the specification, differentiation and function of multiciliated cells in vertebrates.}, journal={Current biology : CB}, year={2014}, month={Oct} }
 @article{the small gtpase rsg1 is important for the cytoplasmic localization and axonemal dynamics of intraflagellar transport proteins._2013, url={https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24192041/?tool=EBI}, DOI={10.1186/2046-2530-2-13}, abstractNote={Cilia are small, microtubule-based protrusions important for development and homeostasis. We recently demonstrated that the planar cell polarity effector protein Fuz is a critical regulator of axonemal intraflagellar transport dynamics and localization. Here, we report our findings on the role of the small GTPase Rsg1, a known binding partner of Fuz, and its role in the dynamics and cytoplasmic localization of intraflagellar transport proteins.We find that Rsg1 loss of function leads to impaired axonemal IFT dynamics in multiciliated cells. We further show that Rsg1 is required for appropriate cytoplasmic localization of the retrograde IFT-A protein IFT43. Finally, we show that Rsg1 governs the apical localization of basal bodies, the anchoring structures of cilia.Our data suggest that Rsg1 is a regulator of multiple aspects of ciliogenesis, including apical trafficking of basal bodies and the localization and dynamics intraflagellar transport proteins.}, journal={Cilia}, year={2013}, month={Oct} }
 @article{control of vertebrate intraflagellar transport by the planar cell polarity effector fuz._2012, url={https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22778277/?tool=EBI}, DOI={10.1083/jcb.201204072}, abstractNote={Cilia play key roles in development and homeostasis, and defects in cilia structure or function lead to an array of human diseases. Ciliogenesis is accomplished by the intraflagellar transport (IFT) system, a set of proteins governing bidirectional transport of cargoes within ciliary axonemes. In this paper, we present a novel platform for in vivo analysis of vertebrate IFT dynamics. Using this platform, we show that the planar cell polarity (PCP) effector Fuz was required for normal IFT dynamics in vertebrate cilia, the first evidence directly linking PCP to the core machinery of ciliogenesis. Further, we show that Fuz played a specific role in trafficking of retrograde, but not anterograde, IFT proteins. These data place Fuz in the small group of known IFT effectors outside the core machinery and, additionally, identify Fuz as a novel cytoplasmic effector that differentiates between the retrograde and anterograde IFT complexes.}, journal={The Journal of cell biology}, year={2012}, month={Jul} }
 @article{competitive inhibition of carcinogen-activating cyp1a1 and cyp1b1 enzymes by a standardized complex mixture of pah extracted from coal tar._2007, url={https://doi.org/10.1002/ijc.22466}, DOI={10.1002/ijc.22466}, abstractNote={AbstractA complex mixture of polycyclic aromatic hydrocarbons (PAH) extracted from coal tar, the Standard Reference Material (SRM) 1597, was recently shown to decrease the levels of DNA binding of the 2 strong carcinogens benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) in the human mammary carcinoma‐derived cell line MCF‐7 (Mahadevan et al., Chem Res Toxicol 2005;18:224–231). The present study was designed to further elucidate the biochemical mechanisms involved in this inhibition process. We examined the effects of SRM 1597 on the metabolic activation of BP and DBP toward DNA‐binding derivatives in Chinese hamster cells expressing either human cytochrome P450 (CYP) 1A1 or CYP1B1. SRM 1597 inhibited BP‐DNA adduct formation through the entire exposure time in cells expressing human CYP1A1, while it significantly inhibited adduct formation only up to 48 hr when co‐treated with DBP. Conversely, human CYP1B1‐expressing cells were unable to catalyze PAH‐DNA adduct formation on treatment with SRM 1597 alone, and on co‐treatment with BP or DBP. The data obtained from biochemical experiments revealed that SRM 1597 competitively inhibited the activity of both human enzymes as analyzed by 7‐ethoxyresorufin O‐deethylation assays. While the Michaelis‐Menten constant (KM) was <0.4 μM in the absence of SRM 1597, this value increased up to 1.12 (CYP1A1) or 4.45 μM (CYP1B1) in the presence of 0.1 μg/ml SRM 1597. Hence the inhibitory effects of the complex mixture on human CYP1B1 were much stronger when compared to human CYP1A1. Taken together, the decreases in PAH‐DNA adduct formation on co‐treatment with SRM 1597 revealed inhibitory effects on the CYP enzymes that convert carcinogenic PAH into DNA‐binding metabolites. The implications for the tumorigenicity of complex environmental PAH mixtures are discussed. © 2006 Wiley‐Liss, Inc.}, journal={International journal of cancer}, year={2007}, month={Mar} }