A Sonic Hedgehog–Independent, Retinoid-Activated Pathway of Neurogenesis in the Ventral Spinal Cord

Sonic hedgehog (Shh) is thought to control the generation of motor neurons and interneurons in the ventral CNS. We show here that a Shh-independent pathway of interneuron generation also operates in the ventral spinal cord. Evidence for this parallel pathway emerged from an analysis of the induction of ventral progenitors that express the Dbx homeodomain proteins and of Evx1/2 (V0) and En1 (V1) neurons. Shh signaling is sufficient to induce Dbx cells and V0 and V1 neurons but is not required for their generation in vitro or in vivo. Retinoids appear to mediate this parallel pathway. These findings reveal an unanticipated Shh-independent signaling pathway that controls progenitor cell identity and interneuron diversity in the ventral spinal cord.