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XB-ART-41359
Development April 1, 2010; 137 (8): 1339-49.

Direct activation of Shroom3 transcription by Pitx proteins drives epithelial morphogenesis in the developing gut.



Abstract
Individual cell shape changes are essential for epithelial morphogenesis. A transcriptional network for epithelial cell shape change is emerging in Drosophila, but this area remains largely unexplored in vertebrates. The distinction is important as so far, key downstream effectors of cell shape change in Drosophila appear not to be conserved. Rather, Shroom3 has emerged as a central effector of epithelial morphogenesis in vertebrates, driving both actin- and microtubule-based cell shape changes. To date, the morphogenetic role of Shroom3 has been explored only in the neural epithelium, so the broad expression of this gene raises two important questions: what are the requirements for Shroom3 in non-neural tissues and what factors control Shroom3 transcription? Here, we show in Xenopus that Shroom3 is essential for cell shape changes and morphogenesis in the developing vertebrate gut and that Shroom3 transcription in the gut requires the Pitx1 transcription factor. Moreover, we show that Pitx proteins directly activate Shroom3 transcription, and we identify Pitx-responsive regulatory elements in the genomic DNA upstream of Shroom3. Finally, we show that ectopic expression of Pitx proteins is sufficient to induce Shroom3-dependent cytoskeletal reorganization and epithelial cell shape change. These data demonstrate new breadth to the requirements for Shroom3 in morphogenesis, and they also provide a cell-biological basis for the role of Pitx transcription factors in morphogenesis. More generally, these results provide a foundation for deciphering the transcriptional network that underlies epithelial cell shape change in developing vertebrates.

PubMed ID: 20332151
PMC ID: PMC2846243
Article link: Development
Grant support: [+]
Genes referenced: shroom3 pitx1 actl6a ag1 pitx3 shroom1 tbx2 tjp1 tuba4b tubg1
Antibodies: Tjp1 Ab1 Tuba4b Ab2 Tubg1 Ab1
Morpholinos: pitx1 MO1 pitx1 MO2 shroom3 MO1


Article Images: [+] show captions
References:
Barrett, 1998, Pubmed [+]


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