Multimodal Hox5 activity generates motor neuron diversity.

Autor: KC, Ritesh, López de Boer, Raquel, Lin, Minshan, Vagnozzi, Alicia N., Jeannotte, Lucie, Philippidou, Polyxeni
Zdroj: Communications Biology; 9/17/2024, Vol. 7 Issue 1, p1-16, 16p
Abstrakt: Motor neurons (MNs) are the final output of circuits driving fundamental behaviors, such as respiration and locomotion. Hox proteins are essential in generating the MN diversity required for accomplishing these functions, but the transcriptional mechanisms that enable Hox paralogs to assign distinct MN subtype identities despite their promiscuous DNA binding motif are not well understood. Here we show that Hoxa5 modifies chromatin accessibility in all mouse spinal cervical MN subtypes and engages TALE co-factors to directly bind and regulate subtype-specific genes. We identify a paralog-specific interaction of Hoxa5 with the phrenic MN-specific transcription factor Scip and show that heterologous expression of Hoxa5 and Scip is sufficient to suppress limb-innervating MN identity. We also demonstrate that phrenic MN identity is stable after Hoxa5 downregulation and identify Klf proteins as potential regulators of phrenic MN maintenance. Our data identify multiple modes of Hoxa5 action that converge to induce and maintain MN identity.In vivo analysis of chromatin accessibility and transcription factor binding reveals multifaceted actions and novel interactors of Hox5 proteins in motor neuron specification [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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