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

The meninges act as a regulator of brain development by secreting ligands
that act on neural cells to regulate neurogenesis and neuronal migration.
Meningeal-derived retinoic acid (RA) promotes neocortical neural
progenitor cell cycle exit; however, the underlying molecular mechanism is
unknown. Here, we used spatial transcriptomics and profiling of
retinoic-acid receptor-α (RARα) DNA binding in Foxc1-mutant embryos that
lack meninges-derived ligands to identify the neurogenic transcriptional
mechanisms of RA signaling in telencephalic neural progenitors. We
determined that meningeal-derived RA controls neurogenesis by suppressing
progenitor 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 Sox2expression, and RA promotes Sox2ot
expression in neocortical progenitors. Our findings elucidate a previously
unknown mechanism of how meningeal RA coordinates neocortical development
and insight into how defects in meningeal development may cause
neurodevelopmental disorders.