Conserved bHLH transcription factors regulate cell-fate decisions and neuronal differentiation in the developing CNS of invertebrates and vertebrates. In Drosophila, Hairy and Enhancer of split [H/E(spl)]bHLH proteins maintain neural progenitors in a proliferative state by antagonizing the activity of proneural bHLH proteins. But, as Guimera and co-workers now report, the H/E(spl)-related mouse protein Megane (Mgn) is required for the differentiation of GABAergic neurons in the superior colliculus, part of the dorsal midbrain (see ). To discover the physiological role of Mgn, the researchers generated Mgn-null mice, which made normal numbers of GABAergic progenitor cells during development but failed to express Gad65 or Gad67 in the superior colliculus; these genes encode the enzymes that synthesize the inhibitory neurotransmitter GABA. As is consistent with a deficit in GABAergic neurons, the mice also developed epilepsy-like symptoms soon after birth. Thus, the researchers propose that vertebrate h/E(spl)-related genes,unlike those in the fly, can be involved in the acquisition of specific neuronal identities.
