Central Nervous System Essay -- Biology, Cells, Retinogenesis

SPECIFIC AIMSThe neural progenitor prison cells give rise to myriad cell types of the central nervous system during development 1. However, the molecular basis of generation of diverse cell types from a single pool of progenitors is largely unknown. As a part of the central nervous system, the neural retina is an nonpareil model system to comprehend this mechanism because its cellular diversity also results from multipotent progenitors, the retinal progenitor cells (RPCs) 2-4. During retinogenesis, RPCs pass through different competent stages, to each one characterized largely by a unique set of transcription factors and defining RPCs ability to generate specific cell types during sequential cell divisions 5-7. This study is an flack to further our understanding of how transcription factors direct RPCs to differentiate into retinal ganglion cells (RGCs), the cell that connect retina to the brain. It is known that the basic helix-turn-helix transcription factor Math-5 renders RPCs the competence to adopt an RGC set 8-10. It essenti solelyy acts by turning on the expression of the POU domain factor Pou4f2 and the LIM homeobox factor Isl1, both critical for RGC differentiation and survival 11-12. However, not all Math5-expressing progenitors become RGCs 13. Nor can Pou4f2 and Isl1 be the only factors governing the terminal differentiation of RGCs as a large proportion of Math-5 controlled genes is not regulated by them 12. What factors sequester RGC fate? What are those non-Pou4f2/Isl1 factors that take part in RGC differentiation? If we are to set a milestone in medicine by using cell replacement therapy to treat neurodegenerative diseases, such fundamental questions like these must be answered. Available evidences suggest that the tra... ...OC factors in RGC development. In the developing liver, OC factors control TGF- signaling 18, 21, which is pro-apoptotic in RGCs 23. Therefore, an Inquiry into the retinal onecut/TGF- connection and its downstream cons equences may further our understanding of the regulation of RGC apoptosis, which is disturbed in several degenerative diseases. Using qPCR, Western blot, and reporter assay, I entrust first assess if retinal TGF- signaling is enhanced in the absence of OC factors. Then using a rescue experiment, I will see if increased TGF- signaling accounts for the retinal phenotype seen in onecut-null mice. Finally, using in situ hybridization, IF staining and reporter assay, I will look into the relationship of OC factors with Math5, Pouf42, and Isl1 to establish their provisional position in the hierarchy of transcription factors that control RGC development.