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bioRxiv · 10.1101/2022.09.23.509112

Nhlh1 and Nhlh2, a global transcriptional mechanism regulating commissural axon projection via activating Robo3

Masuda, A.·Ajima, R.·Saga, Y.·Hirata, T.·Zhu, Y.
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Abstract

SUMMARYCommissural neurons are highly heterogeneous in their developmental origins, neurotransmitter type and function, but all share the common feature of projecting axons across the midline. The floor plate-crossing commissural axons in mammals, from the spinal cord to the midbrain, are guided by a conserved molecular mechanism relying primarily on Netrin-1/DCC/Robo3 signaling. Up to date, we know very little about the upstream transcriptional program that specify commissural axon laterality, neither do we know if a common mechanism operates in all commissural neurons. Here, we identified a pair of highly related helix-loop-helix transcription factors, Nhlh1 and Nhlh2, as a global transcriptional mechanism that controls the laterality of all floor plate-crossing commissural axons. Forced expression of Nhlh1/2 induce ectopic Robo3 expression and contralateral axon projections. And mutant mice deficient in both genes show a remarkable reduction in Robo3 expression and a total lack of ventral commissures from the spinal cord to the midbrain. This global mechanism may interact with neuron type specific mechanism to achieve specific generation of commissural circuits.

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Masuda, A., Ajima, R., Saga, Y., Hirata, T., Zhu, Y.. 2022-09-23. Nhlh1 and Nhlh2, a global transcriptional mechanism regulating commissural axon projection via activating Robo3. https://doi.org/10.1101/2022.09.23.509112

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