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Constitutive activation of canonical Wnt signaling in hem progenitors suppresses the fate of hem-derived Cajal-Retzius cells

ABSTRACT: Cajal-Retzius cells (CR cells) are the earliest born neurons in the cerebral cortex, and have been implicated in neuronal migration and development of cortical circuitry. One of the sources of CR cells is the cortical hem, which is rich in morphogens of the canonical WNT signaling family. In this study we examine the effect of stabilization of β-CATENIN (gain of function, GOF) in the mouse cortical hem and show that although neurons are still produced, they do not acquire a CR cell identity. The trajectory of differentiation examined using single-cell transcriptomics revealed that upon β-CATENIN GOF, hem-derived CR cells do not display a TBR2+ stage characteristic of immature CR cells. This effect is only seen when β-CATENIN GOF is driven in hem progenitors and is not seen upon β-CATENIN GOF in postmitotic CR cells. These data suggest that a TBR2+ stage may be important for hem-derived CR cell development and that this step appears to be sensitive to levels of stabilized β-CATENIN in hem progenitors.

ORGANISM(S): Mus musculus

PROVIDER: GSE273962 | GEO | 2026/03/23

REPOSITORIES: GEO

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