Dataset Information

Requirements for Jag1-Rbpj mediated Notch signaling during early mouse lens development.

ABSTRACT:

Background

During vertebrate lens development, the lens placode in the embryonic ectoderm invaginates into a lens vesicle, which then separates from the surface epithelium, followed by two waves of fiber cell differentiation. In the mouse, multiple labs have shown that Jag1-Notch signaling is critically required during the second wave of lens fiber cell formation. However, Notch signaling appears to play no obvious role during lens induction or morphogenesis, although multiple pathway genes are expressed at these earlier stages.

Results

Here, we explored functions for Notch signaling specifically during early lens development, by using the early-acting AP2α-Cre driver to delete Jag1 or Rbpj. We found that Jag1 and Rbpj are not required during lens induction, but are necessary for proper lens vesicle separation from the surface ectoderm.

Conclusions

We conclude that precise levels of Notch signaling are essential during lens vesicle morphogenesis. In addition, AP2α-Cre-mediated deletion of Rbpj resulted in embryos with cardiac outflow tract and liver deformities, and perinatal lethality.

SUBMITTER: Le TT

PROVIDER: S-EPMC3288604 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Publications

Requirements for Jag1-Rbpj mediated Notch signaling during early mouse lens development.

Le Tien T TT Conley Kevin W KW Mead Timothy J TJ Rowan Sheldon S Yutzey Katherine E KE Brown Nadean L NL

Developmental dynamics : an official publication of the American Association of Anatomists 20120125 3

<h4>Background</h4>During vertebrate lens development, the lens placode in the embryonic ectoderm invaginates into a lens vesicle, which then separates from the surface epithelium, followed by two waves of fiber cell differentiation. In the mouse, multiple labs have shown that Jag1-Notch signaling is critically required during the second wave of lens fiber cell formation. However, Notch signaling appears to play no obvious role during lens induction or morphogenesis, although multiple pathway ge ...[more]

PMID: 22275127

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Project description:BackgroundMammalian early embryo development requires a well-orchestrated interplay of cell signaling pathways. Notch is a major regulatory pathway involved in cell-fate determination in embryonic and adult scenarios. However, the role of Notch in embryonic pre-implantation development is controversial. In particular, Notch role on blastocyst development and hatching remains elusive, and a complete picture of the transcription and expression patterns of Notch components during this time-period is not available.ResultsThis study provided a comprehensive view on the dynamics of individual embryo gene transcription and protein expression patterns of Notch components (receptors Notch1-4; ligands Dll1 and Dll4, Jagged1-2; and effectors Hes1-2), and their relationship with transcription of gene markers of pluripotency and differentiation (Sox2, Oct4, Klf4, Cdx2) during mouse blastocyst development and hatching. Transcription of Notch1-2, Jagged1-2 and Hes1 was highly prevalent and dynamic along stages of development, whereas transcription of Notch3-4, Dll4 and Hes2 had a low prevalence among embryos. Transcription levels of Notch1, Notch2, Jagged2 and Hes1 correlated with each other and with those of pluripotency and differentiation genes. Gene transcription was associated to protein expression, except for Jagged2, where high transcription levels in all embryos were not translated into protein. Presence of Notch signaling activity was confirmed through nuclear NICD and Hes1 detection, and downregulation of Hes1 transcription following canonical signaling blockade with DAPT. In vitro embryo culture supplementation with Jagged1 had no effect on embryo developmental kinetics. In contrast, supplementation with Jagged2 abolished Jagged1 transcription, downregulated Cdx2 transcription and inhibited blastocyst hatching. Notch signaling blockade by DAPT downregulated transcription of Sox2, and retarded embryo hatching.ConclusionTranscription of Notch genes showed a dynamic pattern along blastocyst development and hatching. Data confirmed Notch signaling activity, and lead to the suggestion that Notch canonical signaling may be operating through Notch1, Notch3, Jagged1 and Hes1. Embryo culture supplementation with Jagged1 and Jagged2 unveiled a possible regulatory effect between Jagged1, Cdx2 and blastocyst hatching. Overall, results indicate that a deregulation in Notch signaling, either by its over or under-activation, affects blastocyst development and hatching.

Dataset Information

Requirements for Jag1-Rbpj mediated Notch signaling during early mouse lens development.

Background

Results

Conclusions

Publications

Requirements for Jag1-Rbpj mediated Notch signaling during early mouse lens development.

Similar Datasets

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