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Genetic And Chemical Dissection Of Bloodbrain Barrier Development In Zebrafish, Robyn Anne Umans Dec 2014

Genetic And Chemical Dissection Of Bloodbrain Barrier Development In Zebrafish, Robyn Anne Umans

Theses and Dissertations (ETD)

The blood-brain barrier (BBB) maintains a homeostatic environment as well as prohibits the entrance of xenobiotics into the brain. Because of these qualities, drug delivery is a fundamental challenge for the treatment of many diseases of the central nervous system (CNS). Along with limiting the access of therapeutics into the brain, the BBB is also impaired in CNS pathologies. Understanding the molecular cues that are essential for healthy BBB development and integrity may reveal targets for drug delivery leading to decreased progression or possible treatment of many detrimental CNS diseases. While the central features of the BBB have been accepted, …


Preliminary Study On How Tumor Suppressor Nf2 Inhibits Transcriptional Coactivators Yap/Taz In The Developing Mouse Brain, Yu He May 2014

Preliminary Study On How Tumor Suppressor Nf2 Inhibits Transcriptional Coactivators Yap/Taz In The Developing Mouse Brain, Yu He

Theses and Dissertations (ETD)

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 …