DRAXIN regulates interhemispheric fissure remodelling to influence the extent of corpus callosum formation
- The University of Queensland, Australia
- University of California, San Francisco, United States
- University of Melbourne and The Royal Childrens Hospital, Australia
Abstract
Corpus callosum dysgenesis (CCD) is a congenital disorder that incorporates either partial or complete absence of the largest cerebral commissure. Remodelling of the interhemispheric fissure (IHF) provides a substrate for callosal axons to cross between hemispheres, and its failure is the main cause of complete CCD. However, it is unclear whether defects in this process could give rise to the heterogeneity of expressivity and phenotypes seen in human cases of CCD. We identify incomplete IHF remodelling as the key structural correlate for the range of callosal abnormalities in inbred and outcrossed BTBR mouse strains, as well as in humans with partial CCD. We identify an eight base-pair deletion in Draxin and misregulated astroglial and leptomeningeal proliferation as genetic and cellular factors for variable IHF remodelling and CCD in BTBR strains. These findings support a model where genetic events determine corpus callosum structure by influencing leptomeningeal-astroglial interactions at the IHF.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures that contain numerical data.
Article and author information
Author details
Funding
National Health and Medical Research Council (GNT1048849)
- Linda J Richards
National Health and Medical Research Council (GNT1126153)
- Linda J Richards
National Institutes of Health (5R01NS058721)
- Elliott H Sherr
- Linda J Richards
Australian Research Council (DE160101394)
- Rodrigo Suárez
Department of Education, Skills and Employment Australia (Research Training Program scholarship)
- Laura Morcom
- Jonathan WC Lim
University of Queensland (Research Scholarship)
- Timothy J Edwards
- Kok-Siong Chen
Queensland Brain Institute (Top-Up Scholarship)
- Laura Morcom
- Timothy J Edwards
- Jonathan WC Lim
National Health and Medical Research Council (GNT1120615)
- Linda J Richards
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Prior approval for all breeding and experiments was obtained from the University of Queensland Animal Ethics Committee and was conducted in accordance with the Australian code for the care and use of animals for scientific purposes. The protocol, experiments and animal numbers were approved under the following project approval numbers: QBI/305/17, QBI/306/17, QBI/311/14 NHMRC (NF), QBI/356/17, and QBI/310/14/UQ (NF).
Human subjects: Ethics for human experimentation was acquired by local ethics committees at The University of Queensland (Australia), and carried out in accordance with the provisions contained in the National Statement on Ethical Conduct in Human Research and with the regulations governing experimentation on humans (Australia), under the following human ethics approvals: HEU 2014000535, and HEU 2015001306.
Copyright
© 2021, Morcom et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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DRAXIN regulates interhemispheric fissure remodelling to influence the extent of corpus callosum formation
eLife 10:e61618.
https://doi.org/10.7554/eLife.61618
