PMID:20332151

Citation	Chung, MI, Nascone-Yoder, NM, Grover, SA, Drysdale, TA and Wallingford, JB (2010) Direct activation of Shroom3 transcription by Pitx proteins drives epithelial morphogenesis in the developing gut. Development 137:1339-49
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.
Links	PubMed PMC2846243 Online version:10.1242/dev.044610
Keywords	Animals; Base Sequence; Blastomeres/physiology; Cell Shape/genetics; Conserved Sequence; DNA Primers; Drosophila/anatomy & histology; Drosophila/physiology; Epithelial Cells/cytology; Epithelial Cells/physiology; Female; Gastrointestinal Tract/embryology; Gastrointestinal Tract/physiology; Gene Expression Regulation, Developmental; Genes, Reporter; Luciferases/genetics; Morphogenesis/physiology; Oligonucleotides, Antisense/pharmacology; Paired Box Transcription Factors/genetics; RNA, Messenger/genetics; Transcription Factors/genetics; Transcription Factors/physiology; Xenopus laevis/embryology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
XENLA:SHRM3		GO:0048546: digestive tract morphogenesis	ECO:0000314:		P		Fig 1 depicts how Shroom3 is is essential for morphogenesis of the developing gut	complete CACAO 5046
XENLA:SHRM3		GO:0003382: epithelial cell morphogenesis	ECO:0000314:		P		Fig 6D depicts Shroom3 expression in the epidermis	complete CACAO 5047

References

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