Neural patterning of the mammalian forebrain - in vitro generation of Hippocampal neurons from mouse and human ES cells.

The mammalian forebrain develops from a sheet of neuroepithelium that is flanked by distinct patterning centers. The Hippocampus, a part of the brain of crucial function for perception, memory and learning - which is disproportionally affected in diseases such as Alzheimers and epilepsy, arise from the secretion of Wnt and Bmp from a patterning center on the medial side of the hemispheres - the cortical hem. The Sasai lab has developed a robust method for neural induction from mouse and human ES cells cal led SFEBq, which enables selective and efficient induction of a large number neuronal subtypes including cortical neurons. Recent efforts have also resulted in efficient generation of cerebellar neurons and cortical hem tissue from mouse ES cells. Based o n these results, we hypothesize that the SFEBq method also can induce differentiation of mouse and human ES cells into hippocampal neurons which can serve as as an in vitro model of hippocampal patterning and differentiation. The accomplishment of this pr oject will therefore not only produce useful neurons for further research on disease-mechanisms/drug-screening, but might also help elucidate mechanisms underlying hippocampal patterning and development, and serve as a first step towards cell-replacement therapy for diseases that affect the hippocampus.