@article{510311c27327400280734020708c4c3c,
title = "Dcc regulates astroglial development essential for telencephalic morphogenesis and corpus callosum formation",
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.",
author = "Laura Morcom and Ilan Gobius and Marsh, {Ashley P.L.} and Rodrigo Su{\'a}rez and Lim, {Jonathan W.C.} and Caitlin Bridges and Yunan Ye and Fenlon, {Laura R.} and Yvrick Zagar and Douglass, {Amelia M.} and Donahoo, {Amber Lee S.} and Thomas Fothergill and Samreen Shaikh and Peter Kozulin and Edwards, {Timothy J.} and Cooper, {Helen M.} and Consortium, {I. R.C.} and Sherr, {Elliott H.} and Alain Ch{\'e}dotal and Leventer, {Richard J.} and Lockhart, {Paul J.} and Richards, {Linda J.}",
note = "Funding Information: We thank Marc Tessier-Lavigne for the Ntn1-lacZ and Dcc knockout mouse lines, and Susan Acker-mann (Jackson Laboratory) for the Dcckanga mouse lines. We thank colleagues for providing the constructs listed. We thank Luke Hammond, Rumelo Amor, Arnaud Guardin, Andrew Thompson and Matisse Jacobs for assistance with microscopy, which was performed in the Queensland Brain Institute{\textquoteright}s Advanced Microscopy Facility. This work was supported by Australian NHMRC grants GNT456027, GNT631466, GNT1048849 and GNT1126153 to LJR and GNT1059666 to PJL and RJL, and US National Institutes of Health grant 5R01NS058721 to ES and LJR. RS received an Australian Research Council DECRA fellowship (DE160101394). APLM, JWCL, and LM were supported by a research training program scholarship (Australian Postgraduate Award). APLM was further supported by a NHMRC Early Career Research Fellowship (GNT1156820). ALSD was supported by an Australian Postgraduate award. ALSD, JWCL, and LM received a Queensland Brain Institute Top-Up Scholarship. LRF was supported by a UQ Development Fellowship, RJL was supported by a Melbourne Children{\textquoteright}s Clinician Scientist Fellowship and LJR was supported by an NHMRC Principal Research Fellowship (GNT1120615). Funding Information: We thank Marc Tessier-Lavigne for the Ntn1-lacZ and Dcc knockout mouse lines, and Susan Acker-mann (Jackson Laboratory) for the Dcckanga mouse lines. We thank colleagues for providing the con-structs listed. We thank Luke Hammond, Rumelo Amor, Arnaud Guardin, Andrew Thompson and Matisse Jacobs for assistance with microscopy, which was performed in the Queensland Brain Insti-tute{\textquoteright}s Advanced Microscopy Facility. This work was supported by Australian NHMRC grants GNT456027, GNT631466, GNT1048849 and GNT1126153 to LJR and GNT1059666 to PJL and RJL, and US National Institutes of Health grant 5R01NS058721 to ES and LJR. RS received an Australian Research Council DECRA fellowship (DE160101394). APLM, JWCL, and LM were supported by a research training program scholarship (Australian Postgraduate Award). APLM was further supported by a NHMRC Early Career Research Fellowship (GNT1156820). ALSD was supported by an Australian Postgraduate award. ALSD, JWCL, and LM received a Queensland Brain Institute Top-Up Schol-arship. LRF was supported by a UQ Development Fellowship, RJL was supported by a Melbourne Children{\textquoteright}s Clinician Scientist Fellowship and LJR was supported by an NHMRC Principal Research Fellowship (GNT1120615). We thank the families and members of the Australian Disorders of the Corpus Callosum (Aus-DoCC) for their support and time in being involved in this research. We thank the International Research Consortium for the Corpus Callosum and Cerebral Connectivity (IRC5, https://www.irc5. org) researchers for discussions and input. Publisher Copyright: {\textcopyright} 2021, eLife Sciences Publications Ltd. All rights reserved.",
year = "2021",
month = apr,
doi = "10.7554/ELIFE.61769",
language = "English",
volume = "10",
journal = "eLife",
issn = "2050-084X",
}