<i>LMX1B</i> missense-perturbation of regulatory element footprints disrupts serotonergic forebrain axon arborization.

ABSTRACT: Pathogenic coding mutations are prevalent in human neuronal transcription factors (TFs) but how they disrupt development is poorly understood. Lmx1b is a master transcriptional regulator of postmitotic Pet1 neurons that give rise to mature serotonin (5-HT) neurons; over two hundred pathogenic heterozygous mutations have been discovered in human LMX1B, yet their impact on brain development has not been investigated. Here, we developed mouse models with different LMX1B DNA-binding missense mutations. Missense heterozygosity broadly altered Pet1 neuron transcriptomes, but expression changes converged on axon and synapse genes. Missense heterozygosity effected highly specific deficits in the postnatal maturation of forebrain serotonin axon arbors, primarily in the h

SUBMITTER: Eastman B 

PROVIDER: S-EPMC11661190 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature