In mammalian brains, the choroid plexus secretes cerebrospinal fluid and functions as a blood-brain barrier. Now, on p. 2531, Imayoshi and colleagues reveal that the Hes genes and neurogenin regulate the specification of this uniquely non-neural brain tissue in mouse embryos. The researchers show that the prospective choroid plexus region in the dorsal telencephalic midline of the developing brain expresses the proneural basic helix-loop-helix(bHLH) gene neurogenin 2 (Ngn2) and the bHLH repressor genes Hes1 and Hes5. This region, they report, gives rise to choroid plexus epithelial cells and to Cajal-Retzius cells, specialised neurons that guide neuronal migration. Inactivation of Hes1 in the dorsal telencephalon of Hes3/Hes5-null mice upregulates Ngn2 expression and leads to increased formation of Cajal-Retzius cells and to a complete loss of choroid plexus epithelial cells; Ngn2overexpression has similar effects. Thus, the researchers conclude, Hes and Ngn2 genes antagonistically regulate non-neural versus neural fate specification in the developing mouse brain, a new role for mammalian bHLH genes.