TY - JOUR
T1 - A global gene regulatory program and its region-specific regulator partition neurons into commissural and ipsilateral projection types
AU - Masuda, Aki
AU - Nishida, Kazuhiko
AU - Ajima, Rieko
AU - Saga, Yumiko
AU - Bakhtan, Marah
AU - Klar, Avihu
AU - Hirata, Tatsumi
AU - Zhu, Yan
N1 - Publisher Copyright:
© 2024 The Authors.
PY - 2024/5/24
Y1 - 2024/5/24
N2 - Understanding the genetic programs that drive neuronal diversification into classes and subclasses is key to understand nervous system development. All neurons can be classified into two types: commissural and ipsilateral, based on whether their axons cross the midline or not. However, the gene regulatory program underlying this binary division is poorly understood. We identified a pair of basic helix-loop- helix transcription factors, Nhlh1 and Nhlh2, as a global transcriptional mechanism that controls the laterality of all floor plate-crossing commissural axons in mice. Mechanistically, Nhlh1/2 play an essential role in the expression of Robo3, the key guidance molecule for commissural axon projections. This genetic program appears to be evolutionarily conserved in chick. We further discovered that Isl1, primarily expressed in ipsilateral neurons within neural tubes, negatively regulates the Robo3 induction by Nhlh1/2. Our findings elucidate a gene regulatory strategy where a conserved global mechanism intersects with neuron class-specific regulators to control the partitioning of neurons based on axon laterality.
AB - Understanding the genetic programs that drive neuronal diversification into classes and subclasses is key to understand nervous system development. All neurons can be classified into two types: commissural and ipsilateral, based on whether their axons cross the midline or not. However, the gene regulatory program underlying this binary division is poorly understood. We identified a pair of basic helix-loop- helix transcription factors, Nhlh1 and Nhlh2, as a global transcriptional mechanism that controls the laterality of all floor plate-crossing commissural axons in mice. Mechanistically, Nhlh1/2 play an essential role in the expression of Robo3, the key guidance molecule for commissural axon projections. This genetic program appears to be evolutionarily conserved in chick. We further discovered that Isl1, primarily expressed in ipsilateral neurons within neural tubes, negatively regulates the Robo3 induction by Nhlh1/2. Our findings elucidate a gene regulatory strategy where a conserved global mechanism intersects with neuron class-specific regulators to control the partitioning of neurons based on axon laterality.
UR - http://www.scopus.com/inward/record.url?scp=85194126319&partnerID=8YFLogxK
U2 - 10.1126/sciadv.adk2149
DO - 10.1126/sciadv.adk2149
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C2 - 38781326
AN - SCOPUS:85194126319
SN - 2375-2548
VL - 10
JO - Science advances
JF - Science advances
IS - 21
M1 - adk2149
ER -