N.O. and S.B. are primary authors with equal contributions.
GABAergic neurons regulate lateral ventricular development via transcription factor Pax5
Article first published online: 25 FEB 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 51, Issue 4, pages 234–245, April 2013
How to Cite
Ohtsuka, N., Badurek, S., Busslinger, M., Benes, F. M., Minichiello, L. and Rudolph, U. (2013), GABAergic neurons regulate lateral ventricular development via transcription factor Pax5. Genesis, 51: 234–245. doi: 10.1002/dvg.22370
The authors declare that there are no potential sources of conflict of interest.
This work was supported by NIMH MERIT AWARD R37 MH042261 Limbic lobe in Schizophrenia and Bipolar Disorder (Principal Investigator: F.M.B.), and an E-STAR fellowship funded by the EC's FP6 Marie Curie Host fellowship for Early Stage Research Training (MEST-CT-2004–504640) to S.B. M.B.'s research was supported by Boehringer Ingelheim.
- Issue published online: 18 APR 2013
- Article first published online: 25 FEB 2013
- Accepted manuscript online: 24 JAN 2013 12:06PM EST
- Manuscript Accepted: 14 JAN 2013
- Manuscript Revised: 9 JAN 2013
- Manuscript Received: 4 MAY 2012
- paired box genes;
- GABA neurons;
Postmortem studies have revealed a downregulation of the transcription factor Pax5 in GABAergic neurons in bipolar disorder, a neurodevelopmental disorder, raising the question whether Pax5 in GABAergic neurons has a role in normal brain development. In a genetic approach to study functions of Pax5 in GABAergic neurons, Pax5 was specifically deleted in GABAergic neurons from Pax5 floxed mice using a novel Gad1-Cre transgenic mouse line expressing Cre recombinase in Gad1-positive, that is, GABAergic neurons. Surprisingly, these mice developed a marked enlargement of the lateral ventricles at approximately 7 weeks of age, which was lethal within 1–2 weeks of its appearance. This hydrocephalus phenotype was observed in mice homozygous or heterozygous for the Pax5 conditional knockout, with a gene dosage-dependent penetrance. By QTL (quantitative trait loci) mapping, a 3.5 Mb segment on mouse chromosome 4 flanked by markers D4Mit237 and D4Mit214 containing approximately 92 genes including Pax5 has previously been linked to differences in lateral ventricular size. Our findings are consistent with Pax5 being a relevant gene underlying this QTL phenotype and demonstrate that Pax5 in GABAergic neurons is essential for normal ventricular development. genesis 51:234–245. © 2013 Wiley Periodicals, Inc.