ArticleScience advances2024
A global gene regulatory program and its region-specific regulator partition neurons into commissural and ipsilateral projection types.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Gene expression programs underlying spinal commissural neuron differentiation and axon growth across the midline.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Temporal control of midline crossing via incoherent feedforward and feedback loops regulating Robo3.iScience · 2026Article
- Spinal circuits encode a map of the trunk to control skin twitches.bioRxiv : the preprint server for biology · 2026Article
- Adaptive loss of function accelerated the evolution of ancient and modern human cognition.bioRxiv : the preprint server for biology · 2026Article
- Dual role of ZIC2 during neural induction: from priming transcription factor to enhancer activator.Nucleic acids research · 2026Article
- Ontogeny of the spinal cord dorsal horn.Science (New York, N.Y.) · 2026Article
- Dissecting the Genetic Basis of Low Back Pain Independent of BMI Through Genomic Structural Equation Modeling.Journal of pain research · 2026Article
- Clinical characteristics and target exploration via scRNA-seq and high-throughput drug screening of FOXO1 fusion positive rhabdomyosarcoma.Pediatric surgery international · 2025Article
- Temporal control of axonal floor plate crossing through a combination of incoherent feedforward and feedback loops of gene regulatory network regulating Robo3 expression.bioRxiv : the preprint server for biology · 2025Article
- Entorhinal cortex layer III Adgrl2 expression controls topographical circuit connectivity required for sequence learning.Translational psychiatry · 2025Article
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8 authors.
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Abstract
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.
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