Conditional induction of Math1 specifies embryonic stem cells to cerebellar granule neuron lineage and promotes differentiation into mature granule neurons.

摘要: Directing differentiation of embryonic stem cells (ESCs) to specific neuronal subtype is critical for modeling disease pathology in vitro. An attractive means action would be combine regulatory factors and extrinsic inductive signals added the culture medium. In this study, we have generated mature cerebellar granule neurons by combining a temporally controlled transient expression Math1, master gene neuron differentiation, with involved development. Using Tetracyclin-On transactivation system, overexpressed Math1 at various stages ESCs found that yield progenitors was considerably increased when induced during body stage. triggered Mbh1 Mbh2, two target genes directly precursor formation strong early territory markers En1 NeuroD1. Three weeks after induction, observed decrease number glial an increase albeit still immature. Combining induction specifically expressed Pde1c, Zic1, GABAα6R characteristic neurons, formed "T-shaped" axons typical synaptic contacts potentials Finally, vivo implantation Math1-induced into young adult mice resulted cell migration settling newly cerebellum. These results show conditional drives toward fate indicate acting on both intrinsic powerful modulate maturation lineage.