RP58 Maintains Neural Progenitor Cells of the Developing Spinal Cord

One of the central questions in the study of neural development is how spinal progenitors produce the vast array of cell types found in the mature nervous system. Progenitors are organized into different domains committed to producing specific types of neurons early in development and, at later times, producing glia. For this progression, progenitors must balance differentiation and maintenance to produce the proper numbers of cells and to retain a progenitor population through development. The transcription factor PLZF, a member of the BTB/POZ gene family, has been implicated as a negative regulator of neurogenesis in early spinal development, and consequently, may serve a role in preserving a progenitor population for astrocyte production at later times in development.  We have identified a closely related gene of the same family, RP58, that partially overlaps in tissue expression with PLZF and is potentially also a negative regulator of neurogenesis. The focus of this study is to begin characterizing the function of RP58 in spinal development by describing its endogenous expression pattern and by manipulating its function using plasmid misexpression and RNA interference approaches. Currently, a short hairpin RNA (shRNA) vector approach is being pursued to investigate the loss of function phenotype of RP58.  Through this combination of gain and loss of function experiments a more comprehensive understanding of RP58’s role in the development of the spinal cord will be developed a long with a greater insight into the role of the BTB/POZ family.