Dual Role of DLK1 in GnRH Neuron Ontogeny.

ABSTRACT: Mutations in Delta Like Non-Canonical Notch Ligand 1 (DLK1), a paternally expressed imprinted gene, underlie central precocious puberty (CPP), yet the mechanism remains unclear. To test the hypothesis that DLK1 plays a role in gonadotropin releasing hormone (GnRH) neuron ontogeny, 75 base pairs were deleted in both alleles of DLK1 exon 3 with CRISPR-Cas9 in human pluripotent stem cells (hPSCs). This line, exhibiting More than 80% loss of DLK1 protein, was differentiated into GnRH neurons by dual SMAD inhibition (dSMADi), FGF8 treatment and Notch inhibition, as previously described, however, it did not exhibit accelerated GNRH1 expression. Activation of (WT) DLK1 with CRISPRa during dSMADi suppressed the formation of anterior neuronal precursors, and almost completely inhibited GnRH neuron

SUBMITTER: Eskici N 

PROVIDER: S-EPMC12504412 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature