@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={Abstract}, 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.}, 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={Abstract}, journal={International journal of cancer}, year={2007}, month={Mar} }