Barhl1 is required for maintenance of a large population of neurons in the zonal layer of the superior colliculus.

The mammalian superior colliculus of the midbrain is a brainstem center that integrates sensorimotor signals involved in the control of orienting behaviors. Its structure is characterized by seven well-organized cellular and fibrous layers associated with distinct physiological properties. To date, however, little is known about the molecular bases governing the lamination, differentiation, and survival of superior collicular neurons. Barhl1 is a homeodomain transcription factor that has been demonstrated to play an essential role in maintaining inner ear hair cells, cerebellar granule cells, and precerebellar neurons. We show here that Barhl1 exhibits a select expression pattern in the superior colliculus with positive neurons largely restricted to the zonal layer, as visualized by the beta-galactosidase activity expressed from the lacZ reporter knocked in the Barhl1 locus. Targeted disruption of Barhl1 results in the loss of a large population of neurons from the zonal layer of the superior colliculus, as indicated by reduced beta-galactosidase staining and marker gene expression as well as by increased apoptotic cell death. Taken together, these data suggest that Barhl1 is crucially required for the survival but not for the specification of zonal layer neurons in the superior colliculus.