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Publication : DCC regulates astroglial development essential for telencephalic morphogenesis and corpus callosum formation.

First Author  Morcom L Year  2021
Journal  Elife Volume  10
PubMed ID  33871356 Mgi Jnum  J:304719
Mgi Id  MGI:6695000 Doi  10.7554/eLife.61769
Citation  Morcom L, et al. (2021) DCC regulates astroglial development essential for telencephalic morphogenesis and corpus callosum formation. Elife 10:e61769
abstractText  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). DCC and 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.
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