Orphan nuclear receptor Nurr1 induces neuron differentiation from embryonic cortical precursor cells via an extrinsic paracrine mechanism.

Nurr1 is an orphan nuclear receptor-type transcription factor (TF) that plays critical roles in midbrain dopamine neuron development. This study demonstrated a novel role for Nurr1 in neuronal/astrocytic differentiation of neural precursor (NP) cells isolated from rat embryonic cortices: overexpression of this TF promoted NP cell differentiation towards neurons at the expense of astrocytic differentiation. Single cell-based lineage analyses and experiments using co-cultures revealed that Nurr1 elicited its neurogenic role in an extrinsic paracrine manner. We defined diffusible factors and downstream neurogenic TFs responsible for the Nurr1-mediated neuronal differentiation.