Molecular Mechanisms of Primary Microcephaly

Yale University, New Haven CT

Investigators

Linked publications, trials & patents

Abstract

DESCRIPTION (provided by applicant): The objective of this application is to examine the molecular mechanisms underlying Autosomal Recessive Primary Microcephaly. It is based on the identification of homozygous mutations in WDR62 in individuals with primary microcephaly and a wide spectrum of structural brain abnormalities and aims to gain mechanistic insights into the biology of WDR62 in mammalian brain development. The proposed research test the hypothesis that WDR62 functions in cortical development by controlling cell cycle dynamics, survival or neural progenitors, and/or migration of neurons. It aims to a) determine the cellular function of WDR62; b) establish the functional interacting partners of WDR62 in the developing brain using proteomic approaches and c) examine the relationship of WDR62 with Wnt signaling in the developing brain. The proposed studies carry basic biological value and take advantage of molecular genetic findings that pointed to WDR62 as an important modulator of basic neurodevelopmental mechanisms and implicated its malfunction in a wide spectrum of severe brain malformations.