Dataset Information

Crucial roles of Foxa2 in mouse anterior-posterior axis polarization via regulation of anterior visceral endoderm-specific genes.

ABSTRACT: Anterior visceral endoderm (AVE) plays essential roles with respect to anterior-posterior axis development in the early mouse embryo. To assess the genetic cascade involved in AVE formation, the cis-regulatory elements directing expression of vertebrate Otx2 genes in the AVE were analyzed via generation of transgenic mice. Otx2 expression in AVE is regulated directly by the forkhead transcription factor, Foxa2. Moreover, Foxa2 is essential for expression of the Wnt antagonists, Dkk1 and Cerl, in visceral endoderm during the pre- to early streak stages; however, Foxa2 appears to be dispensable for subsequent Dkk1 expression associated with forebrain induction. Thus, we propose that Foxa2 is crucial in early anterior-posterior axis polarization in terms of regulation of expression of AVE-specific genes. These findings provide profound insights into conserved roles of Foxa2 transcription factors in anterior specification throughout the evolution of the chordate body plan.

SUBMITTER: Kimura-Yoshida C

PROVIDER: S-EPMC1851592 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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Crucial roles of Foxa2 in mouse anterior-posterior axis polarization via regulation of anterior visceral endoderm-specific genes.

Kimura-Yoshida Chiharu C Tian E E Nakano Hiroshi H Amazaki Saori S Shimokawa Kayo K Rossant Janet J Aizawa Shinichi S Matsuo Isao I

Proceedings of the National Academy of Sciences of the United States of America 20070326 14

Anterior visceral endoderm (AVE) plays essential roles with respect to anterior-posterior axis development in the early mouse embryo. To assess the genetic cascade involved in AVE formation, the cis-regulatory elements directing expression of vertebrate Otx2 genes in the AVE were analyzed via generation of transgenic mice. Otx2 expression in AVE is regulated directly by the forkhead transcription factor, Foxa2. Moreover, Foxa2 is essential for expression of the Wnt antagonists, Dkk1 and Cerl, in ...[more]

PMID: 17389379

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Project description:The visceral endoderm (VE) is a simple epithelium that forms the outer layer of the egg-cylinder stage mouse embryo. The anterior visceral endoderm (AVE), a specialised subset of VE cells, is responsible for specifying anterior pattern. AVE cells show a stereotypic migratory behaviour within the VE, which is responsible for correctly orientating the anterior-posterior axis. The epithelial integrity of the VE is maintained during the course of AVE migration, which takes place by intercalation of AVE and other VE cells. Though a continuous epithelial sheet, the VE is characterised by two regions of dramatically different behaviour, one showing robust cell movement and intercalation (in which the AVE migrates) and one that is static, with relatively little cell movement and mixing. Little is known about the cellular rearrangements that accommodate and influence the sustained directional movement of subsets of cells (such as the AVE) within epithelia like the VE. This study uses an interdisciplinary approach to further our understanding of cell movement in epithelia. Using both wild-type embryos as well as mutants in which AVE migration is abnormal or arrested, we show that AVE migration is specifically linked to changes in cell packing in the VE and an increase in multi-cellular rosette arrangements (five or more cells meeting at a point). To probe the role of rosettes during AVE migration, we develop a mathematical model of cell movement in the VE. To do this, we use a vertex-based model, implemented on an ellipsoidal surface to represent a realistic geometry for the mouse egg-cylinder. The potential for rosette formation is included, along with various junctional rearrangements. Simulations suggest that while rosettes are not essential for AVE migration, they are crucial for the orderliness of this migration observed in embryos. Our simulations are similar to results from transgenic embryos in which Planar Cell Polarity (PCP) signalling is disrupted. Such embryos have significantly reduced rosette numbers, altered epithelial packing, and show abnormalities in AVE migration. Our results show that the formation of multi-cellular rosettes in the mouse VE is dependent on normal PCP signalling. Taken together, our model and experimental observations suggest that rosettes in the VE epithelium do not form passively in response to AVE migration. Instead, they are a PCP-dependent arrangement of cells that acts to buffer the disequilibrium in cell packing generated in the VE by AVE migration, enabling AVE cells to migrate in an orderly manner.

Dataset Information

Crucial roles of Foxa2 in mouse anterior-posterior axis polarization via regulation of anterior visceral endoderm-specific genes.

Publications

Crucial roles of Foxa2 in mouse anterior-posterior axis polarization via regulation of anterior visceral endoderm-specific genes.

Similar Datasets

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