Autism, Intellectual Disability

Distal mRNA localization and translation in neural stem cells during mammalian cortical development
2013 Seed Grant
Debra Silver, Ph.D.
Department of Molecular Genetics and Microbiology
Duke University

Cell division is a fundamental mechanism used by stem cells to produce more differentiated cells.  In the developing brain neural progenitors generate both neurons and progenitors during a process called neurogenesis. This process is critical for shaping the proper size, structure and function of the adult brain. When neurogenesis is aberrant, a number of neurodevelopmental disorders can arise, including microcephaly (reduced brain size), intellectual disability, and autism. We lack a fundamental understanding of how neural stem cells generate differentiated cells. In many organisms, localization of mRNAs has emerged as a conserved mechanism influencing progenitor division. Dr. Silver’s lab will test the novel hypothesis that mRNAs are asymmetrically localized and translated within basal structures of neural stem cells. They will apply innovative approaches using a tagged ribosomal protein and a tagged RNA binding protein, FMRP, to perform screens to identify genome-wide mRNAs asymmetrically localized within neural stem cells of the developing brain. Upon completion of these studies they will uncover new molecules that we predict will be critical for cell fate specification in the developing brain.  Dr. Silver anticipates these studies will open up an entirely new field of research related to regulation of neurogenesis. Moreover it will help elucidate fundamental information critical for understanding the etiology and pathology of broad neurodevelopmental disorders.