Date of Award

5-2014

Document Type

Thesis

Degree Name

Master of Science (MS)

Program

Biomedical Sciences

Track

Neuroscience

Research Advisor

Xinwei Cao, Ph.D.

Committee

Kristin Marie Hamre, Ph.D. Junmin Peng, Ph.D.

Keywords

Brain development, Hippo signaling, Nf2/Merlin, Yap/Taz

Abstract

Normal brain development requires precise coordination of neural progenitor proliferation and differentiation, the mechanism of which is not well known. Recently the tumor suppressor neurofibromatosis 2 (Nf2) was shown to regulate the balance of neural progenitor proliferation and differentiation in the developing mouse brain through the Hippo pathway effectors, transcriptional coactivators Yap/Taz. The molecular mechanism of how Nf2 regulates Yap/Taz is not understood. Here I showed that Nf2 regulated the Yap/Taz activity by decreasing the stability of Yap/Taz. The regulation was independent of Yap-S366 phosphorylation, which is required for Yap degradation. I also showed that Nf2 did not regulate Lats1/2 kinases activity. Finally I found Nf2 interacted with Yap in mouse embryonic brain and identified the domains that were required for Nf2-Yap interaction. My study suggests that Nf2 may regulate Yap/Taz independent of the canonical Hippo pathway in the developing mammalian brain.

DOI

10.21007/etd.cghs.2014.0130

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