We propose to elucidate the genetic mechanisms that contribute to patterning of ceils at the cortical-striatal border (CSB), a transient boundary in the developing telencephalon. The CSB is a source of cells that migrate to the basal telencephalic limbic system along the lateral cortical stream (LCS). Understanding the genetic patterning of this region will provide insight into the generation of cells that contribute to the amygdala. We hypothesize that the Ets family transcription factors (Er81 and Erm) and the secreted molecules Tgfa and Fgf7 are genetic downstream targets of the Gsh2/Pax6 patterning events that initially establish the border. We hypothesize that Fgf7 and Tgfa have specific roles in maintenance of border characteristics, and/or specification of neural progenitor cells that are generated at the CSB, via regulation of the Ets genes. Thus, transgenic mice lacking Fgf7 and Tgfa will display disrupted expression of Er81 and Erm, as well as other markers of the CSB (e.g. Sfrp2 and Dbx1), resulting in an alteration of the LCS and subsequent disruption of amygdala development. We will use in situ hybridization for specific genetic markers of the border and immunohistochemistry for cellular subtypes to explicate these patterning events.
| Cocas, Laura A; Miyoshi, Goichi; Carney, Rosalind S E et al. (2009) Emx1-lineage progenitors differentially contribute to neural diversity in the striatum and amygdala. J Neurosci 29:15933-46 |
