A role for borg5 during trophectoderm differentiation.
Stem cell differentiation is accompanied by a gradual cellular morphogenesis and transcriptional changes. Identification of morphological regulators that control cell behavior during differentiation could shed light on how cell morphogenesis is coupled to transcriptional changes during development. By analyzing cellular behavior during differentiation of mouse embryonic stem cells (ESCs), we uncover a role of Borg5 (binder of Rho guanosine 5'-triphosphatase 5) in regulating trophectoderm (TE) cell morphogenesis. We report that differentiation of ESCs toward TE is accompanied by enhanced actin protrusion and cell motility that require upregulation of Borg5. Borg5 interacts with both Cdc42 and atypical protein kinase C (aPKC) and functions downstream of Cdc42 to enhance TE cell motility. Borg5 is required for the sorting of differentiating TE to the outside of ESCs in vitro. In developing embryos, Borg5 protein localizes to cell-cell contacts and the cytoplasm after compaction. It exhibits higher levels of expression in outer cells than in inner cells in morula and blastocysts. Reduction of Borg5 disrupts aPKC localization and inhibits blastocyst formation. Since Cdx2 and Borg5 facilitate each other's expression as ESCs differentiate toward TE, we propose that cell morphogenesis is coupled with transcriptional changes to regulate TE differentiation. Our studies also demonstrate the utility of ESCs in identifying morphological regulators important for development.
Vong
Queenie P
QP
Department of Embryology, Carnegie Institution for Science, Baltimore, Maryland, USA.
Liu
Zhonghua
Z
Yoo
Jae Gyu
JG
Chen
Rong
R
Xie
Wen
W
Sharov
Alexei A
AA
Fan
Chen-Ming
CM
Liu
Chengyu
C
Ko
Minoru S H
MS
Zheng
Yixian
Y
D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D002450:Cell Communication; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D004475:Ectoderm / Q000166:cytology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C551798:Cdc42ep1 protein, mouse; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins