Motor Neurons

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.

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…