Skip to main content
Open Access Publications from the University of California

UC Santa Cruz

UC Santa Cruz Previously Published Works bannerUC Santa Cruz

DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/β-catenin signaling.

  • Author(s): Martin, P-M;
  • Stanley, RE;
  • Ross, AP;
  • Freitas, AE;
  • Moyer, CE;
  • Brumback, AC;
  • Iafrati, J;
  • Stapornwongkul, KS;
  • Dominguez, S;
  • Kivimäe, S;
  • Mulligan, KA;
  • Pirooznia, M;
  • McCombie, WR;
  • Potash, JB;
  • Zandi, PP;
  • Purcell, SM;
  • Sanders, SJ;
  • Zuo, Y;
  • Sohal, VS;
  • Cheyette, BNR
  • et al.

Published Web Location
No data is associated with this publication.

Mice lacking DIX domain containing-1 (DIXDC1), an intracellular Wnt/β-catenin signal pathway protein, have abnormal measures of anxiety, depression and social behavior. Pyramidal neurons in these animals' brains have reduced dendritic spines and glutamatergic synapses. Treatment with lithium or a glycogen synthase kinase-3 (GSK3) inhibitor corrects behavioral and neurodevelopmental phenotypes in these animals. Analysis of DIXDC1 in over 9000 cases of autism, bipolar disorder and schizophrenia reveals higher rates of rare inherited sequence-disrupting single-nucleotide variants (SNVs) in these individuals compared with psychiatrically unaffected controls. Many of these SNVs alter Wnt/β-catenin signaling activity of the neurally predominant DIXDC1 isoform; a subset that hyperactivate this pathway cause dominant neurodevelopmental effects. We propose that rare missense SNVs in DIXDC1 contribute to psychiatric pathogenesis by reducing spine and glutamatergic synapse density downstream of GSK3 in the Wnt/β-catenin pathway.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content

This item is under embargo until December 31, 2999.