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.

Public Health Relevance

The proposed work examines the biological role of a novel protein implicated in primary microcephaly, a disorder characterized by small size of the head and the brain. Findings in human patients with microcephaly suggest that, when not functioning properly, this protein affects the development of the brain, resulting in a variety of structural abnormalities and mental retardation. Understanding the mechanism(s) underlying these observations is the goal of the proposed work.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD075822-02
Application #
8617855
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Parisi, Melissa
Project Start
2013-04-01
Project End
2018-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
2
Fiscal Year
2014
Total Cost
$335,814
Indirect Cost
$134,124
Name
Yale University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520