Although Hox genes specify the anterior-posterior difference in the differentiation of neuronal subtypes, their mode of action is not entirely understood. Using two subtypes of the touch receptor neurons (TRNs) in C. elegans, we found that "posterior induction" underlies the Hox control of terminal neuronal differentiation. The anterior TRNs maintain a default TRN state, whereas the posterior TRNs undergo further morphological and transcriptional differentiation because of the posterior Hox proteins, mainly EGL-5/Abd-B. Misexpression of EGL-5 in the anterior TRNs cause them to differentiate more like the posterior cells. Finally, EGL-5 is required for subtype-specific circuit formation by acting in both the sensory neuron and downstream interneuron to promote functional connectivity. Our studies suggest that Hox proteins regulate subtype diversification of neurons that share the same general cell fate.
Zheng C, Diaz-Cuadros M, and Chalfie M. Hox Genes Promote Neuronal Subtype Diversification through Posterior Induction in Caenorhabditis elegans. Neuron. 2015 Nov 4;88(3):514-27.