GABAergic and glutamatergic neurons are the principal inhibitory and excitatory neurons in the brain, respectively. Selector genes that determine which neurotransmitter phenotype a neuron adopts during development have been identified for some regions of the brain. Now, Nakatani and colleagues report that the basic helix-loop-helix (bHLH) transcriptional repressor gene Helt (also known as Heslike and Megane) promotes GABAergic fate throughout the developing mouse midbrain by repressing the proneural Ngn genes (see p. 2783). The researchers show that glutamatergic neurons replace GABAergic neurons in the midbrain of Helt-deficient mice. Ectopic expression of Helt, they report, has the opposite effect. Neither Helt manipulation, however, affects progenitor domain formation,which indicates that Helt does not specify neuronal identity. In other experiments, the researchers show that Helt promotes a GABAergic fate by suppressing the expression of Ngn1 and Ngn2, bHLH factors that are expressed in glutamatergic progenitors. Thus, they conclude, a bHLH transcription factor network determines the neurotransmitter phenotype of neurons in the midbrain.
Helt! Who goes there?
Helt! Who goes there?. Development 1 August 2007; 134 (15): e1503. doi:
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