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bioRxiv · 10.1101/2022.05.05.490791

Maintenance of neurotransmitter identity by Hox proteins through a homeostatic mechanism

Feng, W.·Destain, H.·Smith, J. J.·Kratsios, P.
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Abstract

Hox transcription factors play fundamental roles during early patterning, but they are also expressed continuously - from embryo through adulthood - in the nervous system. The functional significance of their sustained expression remains unclear. In C. elegans motor neurons (MNs), we find that LIN-39 (Scr/Dfd/Hox4-5) is continuously required during post-embryonic life to maintain neurotransmitter identity, a core element of neuronal function. LIN-39 acts directly to co-regulate genes that define cholinergic identity (e.g., unc-17/VAChT, cho-1/ChT). We further show that LIN-39, MAB-5 (Antp/Hox6-8) and the transcription factor UNC-3 (Collier/Ebf) operate in a positive feedforward loop to ensure continuous and robust expression of cholinergic identity genes. Finally, we identify a two-component, design principle (Hox transcriptional autoregulation counterbalanced by negative UNC-3 feedback) for homeostatic control of Hox gene expression in adult MNs. These findings uncover a noncanonical role for Hox proteins during post-embryonic life, critically broadening their functional repertoire from early patterning to the control of neurotransmitter identity.

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Feng, W., Destain, H., Smith, J. J., Kratsios, P.. 2022-05-05. Maintenance of neurotransmitter identity by Hox proteins through a homeostatic mechanism. https://doi.org/10.1101/2022.05.05.490791

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