Date of Award
Master of Science (MS)
Xinwei Cao, Ph.D.
Kristin Marie Hamre, Ph.D. Junmin Peng, Ph.D.
Brain development, Hippo signaling, Nf2/Merlin, Yap/Taz
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.
He, Yu , "Preliminary Study on How Tumor Suppressor Nf2 Inhibits Transcriptional Coactivators Yap/Taz in the Developing Mouse Brain" (2014). Theses and Dissertations (ETD). Paper 105. http://dx.doi.org/10.21007/etd.cghs.2014.0130.