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Meningeal-derived retinoic acid regulates neurogenesis via suppression of Notch and Sox2 [Spatial Transcriptomics]

ABSTRACT: During development, the meninges act as a regulator of neocortical development by secreting ligands that act on neural cells to regulate neurogenesis and neuronal migration. Meninges-derived retinoic acid (RA) promotes neocortical progenitor cell cycle exit however the underlying mechanism is unknown. Here, we use Foxc1-mutant embryos that lack meninges-derived ligands, spatial transcriptomics, and profiling of retinoic-acid receptor-a (RARa) DNA binding to identify the neurogenic transcriptional mechanisms of RA signaling in cortical neural progenitors. We determined that meningeal-derived RA controls neurogenesis by suppressing self-renewal pathways Notch signaling and the transcription factor Sox2. We show that RARα binds in the Sox2ot promoter, a long non-coding RNA that regulates Sox2 expression, and RA promotes Sox2ot expression in neocortical progenitors. Our findings elucidate a previously unknown mechanism of howmeningeal RA coordinates neocortical development and insight into how defects in meningeal develop can cause neurodevelopmental disorders.

ORGANISM(S): Mus musculus

PROVIDER: GSE269283 | GEO | 2024/09/25

REPOSITORIES: GEO

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Meningeal-derived retinoic acid regulates neurogenesis via suppression of Notch and Sox2 [CUT&Run]

Project description:During development, the meninges act as a regulator of neocortical development by secreting ligands that act on neural cells to regulate neurogenesis and neuronal migration. Meninges-derived retinoic acid (RA) promotes neocortical progenitor cell cycle exit however the underlying mechanism is unknown. Here, we use Foxc1-mutant embryos that lack meninges-derived ligands, spatial transcriptomics, and profiling of retinoic-acid receptor-a (RARa) DNA binding to identify the neurogenic transcriptional mechanisms of RA signaling in cortical neural progenitors. We determined that meningeal-derived RA controls neurogenesis by suppressing self-renewal pathways Notch signaling and the transcription factor Sox2. We show that RARα binds in the Sox2ot promoter, a long non-coding RNA that regulates Sox2 expression, and RA promotes Sox2ot expression in neocortical progenitors. Our findings elucidate a previously unknown mechanism of howmeningeal RA coordinates neocortical development and insight into how defects in meningeal develop can cause neurodevelopmental disorders.

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Meningeal-derived retinoic acid regulates neurogenesis via suppression of Notch and Sox2

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Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity [II]

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