During nervous system development, combinatorial codes of transcription factors specify different neuronal subclasses. But how is each neuron's identity within a subclass specified? Garces and Thor provide new insights into this question by reporting that a unique genetic cascade specifies the fate of the aCC motoneuron in Drosophila, one of seven unique motoneurons in the intersegmental motor nerve (ISN; see p. ). Neurons of the ISN neuronal subclass express the regulatory factors even-skipped and zfh1 (which specify this subclass), and grain, a GATA transcription factor. Although these regulators are expressed by all seven ISN motoneurons, the researchers show that they only act together in a genetic cascade (in which even-skipped regulates grain, which regulates zfh1) to specify the aCC motoneuron – the first,pioneer, neuron to innervate this nerve's target muscle. Why this cascade is only active in the aCC motoneuron is unclear but might depend on the history of each ISN motoneuron.
