Dual Role of DLK1 in GnRH Neuron Ontogeny.

This study used CRISPR-Cas9 to delete 75 base pairs in both alleles of DLK1 exon 3 in human pluripotent stem cells, resulting in over 80% loss of DLK1 protein. The mutant cells were then differentiated into GnRH neurons, but did not exhibit accelerated GNRH1 expression. Conversely, activating wild-type DLK1 early suppressed anterior neuronal precursor formation and GnRH neuron fate, while activating it later significantly increased GNRH1 expression and GnRH secretion. These findings suggest that central precocious puberty caused by DLK1 mutations may act upstream or downstream of GnRH neurons, and highlight the importance of DLK1 expression timing in GnRH neuron development.