Neuronal specification in C. elegans: combining lineage inheritance with intercellular signaling

The nervous system is composed of a high diversity of neuronal types. How this diversity is generated during development is a key question in neurobiology. Addressing this question is one of the reasons that led Sydney Brenner to develop the nematode C. elegans as a model organism. While there was initially a debate on whether the neuronal specification follows a 'European' model (determined by ancestry) or an 'American' model (determined by intercellular communication), several decades of research have established that the truth lies somewhere in between. Neurons are specified by the combination of transcription factors inherited from the ancestor cells and signaling between neighboring cells (especially Wnt and Notch signaling). This converges to the activation in newly generated postmitotic neurons of a specific set of terminal selector transcription factors that initiate and maintain the differentiation of the neuron. In this review, we also discuss the evolution of these specification mechanisms in other nematodes and beyond.