Research Summary

Analysis of the neuron-glia cell fate switch in the medial forebrain: Role of Wnt and Bmp signaling

Analyzing the role of Wnt and Bmp signaling in the neuron-glia cell fate switch in the medial forebrain: During vertebrate CNS development, progenitor cells generate both neurons and glia in sequential order with neurogenesis preceding gliogenesis. The interactive role of extrinsic (secreted morphogens) and intrinsic factors (transcription factors) in affecting the transition of progenitor cells into neurons or glia in the hippocampus is not well understood. The hippocampal primordium, located in the medial telencephalon, is a region of high Wnt and Bmp activity. Wnts are known to act as positive inducers of neurogenesis and inhibitors of astrogliogenesis in multiple systems including the adult hippocampus and the developing cortex. Bmps, in contrast, are known to promote gliogenesis. I want to explore the role of these extrinsic cues in regulating the switch from neurogenesis to astrogliogenesis in the developing hippocampus and their epistatic relation with known inducers of astrogliogenesis (Notch). I will also use live imaging to examine the cell division pattern of normal and induced astrogliogenesis in the hippocampus. Finally, I will examine the Thalamic Eminence (TE) which, like the hippocampus, is very close to the Wnt rich cortical hem, but appears to suppress Wnt signaling (an observation I made during my thesis). I want to explore the functions of Wnts and Bmp molecules in the TE.

Figure Legend: A typical slice culture of the embryonic mouse hippocampus with electroporated GFP+ve cells shown in green. Brains have been electroporated at E15.5 and the slices have been cultured for 7 days in vitro.