Mutations in several genes have now been identified to cause a massive and specific reduction in the total number of neurons in the human brain. The specific role of these primary microcephaly (MCPH) genes in neural progenitors has yet to be fully defined. We have found that that the products of these genes, MCPH proteins, are localized to the point of abscission in dividing cells, and we hypothesize that asymmetric cell abscission in neocortical progenitors is regulated by interactions between MCPH proteins. We will pursue this hypothesis by addressing 4 specific aims: 1) Define the complex of microcephaly proteins at the midbody ring during neurogenesis;2) Examine the role of microcephaly proteins in the timing and location of cell abscissions in neural progenitors;3) Determine the effects of midbody ring inheritance on subsequent neural progenitor outcomes;4) Identify mechanisms that link cell abscissions to apical junctions in neocortical neuroepithelium.

Public Health Relevance

Mutations in several genes have now been identified to cause a massive and specific reduction in the total number of neurons in the human brain. The specific role of these primary microcephaly (MCPH) genes in neural progenitors has yet to be fully defined. We have found that that the products of these genes, MCPH proteins, are localized to the point of abscission in dividing cells, and we hypothesize that asymmetric cell abscission in neocortical progenitors is regulated by interactions between MCPH proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH056524-15
Application #
8325653
Study Section
Neurogenesis and Cell Fate Study Section (NCF)
Program Officer
Panchision, David M
Project Start
1997-02-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
15
Fiscal Year
2012
Total Cost
$340,808
Indirect Cost
$118,058
Name
University of Connecticut
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
614209054
City
Storrs-Mansfield
State
CT
Country
United States
Zip Code
06269
Chen, Fuyi; Becker, Albert; LoTurco, Joseph (2016) Overview of Transgenic Glioblastoma and Oligoastrocytoma CNS Models and Their Utility in Drug Discovery. Curr Protoc Pharmacol 72:14.37.1-12
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