Coordination of sonic hedgehog and Wnt signaling determines ventral and dorsal telencephalic neuron types from human embryonic stem cells

摘要: The directed differentiation of forebrain neuronal types from human embryonic stem cells (hESCs) has not been achieved. Here, we show that hESCs differentiate to telencephalic progenitors with a predominantly dorsal identity in chemically defined medium without known morphogens. This is attributed endogenous Wnt signaling, which upregulates the truncated form GLI3, repressor sonic hedgehog (SHH). A high concentration SHH, or inhibition by dickkopf 1 (DKK1) together low almost completely converts primitive precursors ventral progenitors, partially achieved through both downregulation GLI3 and upregulation full-length expression. These functional glutamatergic GABAergic neurons, respectively. Thus, although generate cells, as opposed other vertebrates, absence exogenous morphogens, use similar molecular mechanism control versus fate. coordination SHH signaling represents novel regulates ventral-dorsal patterning development subtypes.