Heterozygous Dab1 Null Mutation Disrupts Neocortical and Hippocampal Development

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Loss-of-function mutations in Reelin and DAB1 signaling pathways disrupt proper neuronal positioning in the cerebral neocortex and hippocampus, but the underlying molecular mechanisms remain elusive. Here, we re-port that heterozygous yotari mice harboring a single autosomal recessive yotari mutation of Dab1 exhibited a thinner neocortical layer 1 than wild-type mice on postnatal day (P)7. However, a birth-dating study suggested that this reduction was not caused by failure of neuronal migration. In utero electroporation-mediated sparse labeling revealed that the superficial layer neurons of heterozygous yotari mice tended to elongate their apical dendrites within layer 2 than within layer 1. In addition, the CA1 pyramidal cell layer in the caudo-dorsal hippo-campus was abnormally split in heterozygous yotari mice, and a birth-dating study revealed that this splitting was caused mainly by migration failure of late-born pyramidal neurons. Adeno-associated virus (AAV)-medi-ated sparse labeling further showed that many pyramidal cells within the split cell had misoriented apical den-drites. These results suggest that regulation of neuronal migration and positioning by Reelin-DAB1 signaling pathways has unique dependencies on Dab1 gene dosage in different brain regions.

Original languageEnglish
Article numberENEURO.0433-22.2023
JournaleNeuro
Volume10
Issue number4
DOIs
Publication statusPublished - 2023 Apr

Keywords

  • Dab1
  • Reelin
  • apical dendrite
  • haploinsufficiency
  • reeler
  • yotari

ASJC Scopus subject areas

  • General Neuroscience

Fingerprint

Dive into the research topics of 'Heterozygous Dab1 Null Mutation Disrupts Neocortical and Hippocampal Development'. Together they form a unique fingerprint.

Cite this