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The Hippo pathway member Nf2 is required for inner cell mass specification
Katie Cockburn1, Steffen Biechele, Jodi Garner
1Department of Molecular Genetics, University of Toronto, ON M5S 1A8, Canada.
Current Biology : CB
|June 25, 2013
Summary
Neurofibromin 2 (Nf2) is essential for early mammalian development, regulating cell fate decisions. Nf2 acts upstream of the Hippo pathway, controlling Yap phosphorylation and ensuring proper segregation of trophectoderm and inner cell mass lineages.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- Early mammalian development involves specifying trophectoderm (TE) and inner cell mass (ICM) lineages.
- The Hippo pathway, involving Lats1/2 kinases and Yap, regulates this cell fate decision.
- Upstream regulators of the Hippo pathway in this context were previously unknown.
Purpose of the Study:
- To identify upstream regulators of the Hippo pathway in the preimplantation embryo.
- To elucidate the role of Nf2/Merlin in TE/ICM specification.
- To understand the mechanism by which Nf2 influences Yap localization and activity.
Main Methods:
- Injection of dominant-negative Nf2 mRNA into preimplantation embryos.
- Generation and analysis of zygotic and maternal-zygotic Nf2 mutant blastocysts.
- Assessment of Yap localization and Cdx2 expression via molecular assays.
Main Results:
- Nf2 is required for Lats1/2-dependent Yap phosphorylation in preimplantation embryos.
- Loss of Nf2 function leads to Yap mislocalization and ectopic Cdx2 expression.
- Maternal-zygotic Nf2 mutants exhibit severe defects in ICM formation and excess TE, causing peri-implantation lethality.
Conclusions:
- Nf2 acts upstream of Yap in the Hippo signaling pathway during early mammalian development.
- Hippo pathway signaling, regulated by Nf2, is crucial for segregating ICM from TE.
- Nf2 is essential for establishing pluripotency and preventing lineage specification errors.
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