eLife (Apr 2021)
DCC regulates astroglial development essential for telencephalic morphogenesis and corpus callosum formation
- Laura Morcom,
- Ilan Gobius,
- Ashley PL Marsh,
- Rodrigo Suárez,
- Jonathan WC Lim,
- Caitlin Bridges,
- Yunan Ye,
- Laura R Fenlon,
- Yvrick Zagar,
- Amelia M Douglass,
- Amber-Lee S Donahoo,
- Thomas Fothergill,
- Samreen Shaikh,
- Peter Kozulin,
- Timothy J Edwards,
- Helen M Cooper,
- IRC5 Consortium,
- Elliott H Sherr,
- Alain Chédotal,
- Richard J Leventer,
- Paul J Lockhart,
- Linda J Richards
Affiliations
- Laura Morcom
- ORCiD
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia
- Ilan Gobius
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia
- Ashley PL Marsh
- ORCiD
- Bruce Lefroy Centre for Genetic Health Research, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia
- Rodrigo Suárez
- ORCiD
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia
- Jonathan WC Lim
- ORCiD
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia
- Caitlin Bridges
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia
- Yunan Ye
- ORCiD
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia
- Laura R Fenlon
- ORCiD
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia
- Yvrick Zagar
- Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France
- Amelia M Douglass
- ORCiD
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia
- Amber-Lee S Donahoo
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia
- Thomas Fothergill
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia
- Samreen Shaikh
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia
- Peter Kozulin
- ORCiD
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia
- Timothy J Edwards
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia; The University of Queensland, Faculty of Medicine, Brisbane, Australia
- Helen M Cooper
- ORCiD
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia
- IRC5 Consortium
- Members and Affiliates of the International Research Consortium for the Corpus Callosum and Cerebral Connectivity (IRC5), Los Angeles, United States
- Elliott H Sherr
- ORCiD
- Departments of Neurology and Pediatrics, Institute of Human Genetics and Weill Institute of Neurosciences, University of California, San Francisco, San Francisco, United States
- Alain Chédotal
- ORCiD
- Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France
- Richard J Leventer
- Department of Paediatrics, University of Melbourne, Parkville, Australia; Neuroscience Research Group, Murdoch Children’s Research Institute, Parkville, Australia; Department of Neurology, University of Melbourne, Royal Children’s Hospital, Parkville, Australia
- Paul J Lockhart
- ORCiD
- Bruce Lefroy Centre for Genetic Health Research, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia
- Linda J Richards
- ORCiD
- The University of Queensland, Queensland Brain Institute, Brisbane, Australia; The University of Queensland, School of Biomedical Sciences, Brisbane, Australia
- DOI
- https://doi.org/10.7554/eLife.61769
- Journal volume & issue
-
Vol. 10
Abstract
The forebrain hemispheres are predominantly separated during embryogenesis by the interhemispheric fissure (IHF). Radial astroglia remodel the IHF to form a continuous substrate between the hemispheres for midline crossing of the corpus callosum (CC) and hippocampal commissure (HC). Deleted in colorectal carcinoma (DCC) and netrin 1 (NTN1) are molecules that have an evolutionarily conserved function in commissural axon guidance. The CC and HC are absent in Dcc and Ntn1 knockout mice, while other commissures are only partially affected, suggesting an additional aetiology in forebrain commissure formation. Here, we find that these molecules play a critical role in regulating astroglial development and IHF remodelling during CC and HC formation. Human subjects with DCC mutations display disrupted IHF remodelling associated with CC and HC malformations. Thus, axon guidance molecules such as DCC and NTN1 first regulate the formation of a midline substrate for dorsal commissures prior to their role in regulating axonal growth and guidance across it.
Keywords
- midline zipper glia
- astrocyte morphology
- agenesis of the corpus
- callosum
- deleted in colorectal cancer
- telencephalic development
