Transcriptional control of epithelial morphogenesis

Chung, Mei-I

Transcriptional control of epithelial morphogenesis

dc.contributor.advisor	Wallingford, John B.
dc.creator	Chung, Mei-I	en
dc.date.accessioned	2014-07-14T18:24:23Z	en
dc.date.issued	2013-05	en
dc.date.submitted	May 2013	en
dc.date.updated	2014-07-14T18:24:24Z	en
dc.description	text	en
dc.description.abstract	How tissues and organs develop into their final shape during embryogenesis is a fascinating and long-standing question in developmental biology. Tissue morphogenesis is driven by a variety of events at the cellular level and individual cell shape change is one of the central morphogenetic engines. Thus, it is crucial to understand what signals specify the correct cell behavior in specific groups of cells during development. For my doctoral studies, I have focused on two cell shape change events, apical constriction and cilia assembly. First, we present data demonstrating that Shroom3 is essential for cell shape changes and morphogenesis in the developing vertebrate gut, where Shroom3 transcription requires the Pitx1 transcription factor. We identified a Pitx-responsive regulatory element in the genomic DNA upstream of Shroom3, and showed that Pitx proteins directly activated Shroom3 transcription in Xenopus. Moreover, we showed that ectopic expression of Pitx proteins was sufficient to induce Shroom3-dependent cytoskeletal reorganization and epithelial cell shape change. These data demonstrated new breadth to the requirements for Shroom3 in morphogenesis, and also provided a cell-biological mechanism for Pitx transcription factors action during morphogenesis. Next, we focused on understanding the transcriptional regulation of ciliogenesis. We first showed that Rfx2 transcription factor broadly controlled ciliogenesis, and by RNA- and ChIP-sequencing, we showed that Rfx2 directly regulated a wide range of genes encoding diverse ciliogenic machinery. Finally, in addition to ciliogenesis regulation, a large number of non-ciliary genes in our Rfx2 dataset led us to identify a novel role of Rfx2 in controlling insertion of multi-ciliated cells into the overlying mucociliary epithelium. Moreover, we showed here that Slit2, a target of Rfx2, was involved in multi-ciliated cell movements, possibly through mediating cortical E-cadherin level. This work allowed us to begin building a genetic network controlling multi-ciliated cells in mucociliary epithelium. Together, we showed a transcriptional regulation of apical constriction driving gut morphogenesis and a comprehensive transcriptional network that governs multi-ciliated cell development.	en
dc.description.department	Cellular and Molecular Biology	en
dc.format.mimetype	application/pdf	en
dc.identifier.uri	http://hdl.handle.net/2152/25166	en
dc.subject	Morphogenesis	en
dc.subject	Shroom3	en
dc.subject	Rfx2	en
dc.subject	Cilia	en
dc.subject	Transcription	en
dc.subject	Xenopus	en
dc.title	Transcriptional control of epithelial morphogenesis	en
dc.type	Thesis	en
thesis.degree.department	Cellular and Molecular Biology	en
thesis.degree.discipline	Cell and Molecular Biology	en
thesis.degree.grantor	The University of Texas at Austin	en
thesis.degree.level	Doctoral	en
thesis.degree.name	Doctor of Philosophy	en