The Role of the Nkx 6.1 and Homeobox Genes in the Control of Motoneuron and Oligodendrocyte Development

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9808126 QIU One of the fundamental goals of developmental neuroscience is to determine how the large variety of distinct cell types in the nervous system become differentiated out of the embryonic neuroepithelium. Dr. Mengsheng Qiu's laboratory is studying the molecular events that instruct naive cells in the developing nervous system to become motor neurons and oligodendrocytes (a type of glial cell) at an early stage of animal development. Recently, Dr. Qiu has identified two novel transcription factors, named Nkx-6.1 and Nkx-6.2, that are specifically synthesized in the neuroepithelial progenitor cells of motor neurons and oligodendrocytes in the ventral part of the embryonic spinal cord. Dr. Qiu's group will study the functional role of these two genes in the control of motor neuron and oligodendrocyte specification and differentiation using two genetic approaches. First, they will delete the Nkx-6.1 and Nkx-6.2 genes from the mouse genome, both separately and in combination, and investigate how the development of motor neurons and oligodendrocytes is affected. This line of research will provide information on whether the Nkx-6.1 and Nkx-6.2 products are necessary for the normal development of motor neurons and oligodendrocytes. Second, they will produce another genetically-altered mouse line in which Nkx-6.1 gene expression can be specifically induced in the undifferentiated neural cells of the dorsal portion of spinal cord. They will then examine if additional motor neurons or oligodendrocytes are produced by dorsal spinal cord cells, which normally do not become motor neurons. This study will inform us whether Nkx-6.1 or Nkx-6.2 gene expression is capable of initiating the entire motor neuron and/or oligodendrocyte developmental program in undifferentiated neuroepithelial cells.