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.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The Role of Microglial Lysosomes in Selective Neuronal Vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the Nervous System Constructs Internal Models of the External World
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the Orchestra of Movement—Functional Role of Striatal Astrocytes in Health and Disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…