Specification and Maturation of Spinal Interneurons
2005 Seed Grant
Kamal Sharma, Ph.D.
The University of Chicago
Neuronal diversity is a hallmark of the vertebrate nervous system. Our goal is to understand how neuronal diversity is generated in the vertebrate embryonic spinal cord. Vertebrate genomes have a limited number of genes. Mechanisms that can amplify the number of pretein insoforms encoded by these genes are likely to playa critical role in specification of multiple neuronal subtypes. Alternative splicing ofpre-mRNAs is one such mechanism. It is estimated that in vertebrates splicing ofpre mRNAs generates a large proportion (30-60%) of mRNAs. Factors that regulate cell type specific alternative splicing of pre-mRNAs are likely to playa critical role in generation of neuronal diversity. We propose to investigate the role of splicing factors in generation of motor neuron diversity in the spinal cord and test whether these factors regulate alternative splicing of pre-mRNAs that encode preteins required for motor neuron development.
At this time stem cells are thought to be the most promising therapy for neurodegenerative diseases. In two devastating disease conditions, ALS and SMA, motor neurons in the spinal cord degenerate. Can these cells be replaced? Our research is focused on understanding how motor neurons are generated. We wish to learn from the embryos how to make motor neurons from simple precursors. Our findings would find direct use in targeting stem cells to a motor neuron fate.