Netrin-DCC signaling regulates corpus callosum formation through attraction of pioneering axons and by modulating Slit2-mediated repulsion.
The left and right sides of the nervous system communicate via commissural axons that cross the midline during development using evolutionarily conserved molecules. These guidance cues have been particularly well studied in the mammalian spinal cord, but it remains unclear whether these guidance mechanisms for commissural axons are similar in the developing forebrain, in particular for the corpus callosum, the largest and most important commissure for cortical function. Here, we show that Netrin1 initially attracts callosal pioneering axons derived from the cingulate cortex, but surprisingly is not attractive for the neocortical callosal axons that make up the bulk of the projection. Instead, we show that Netrin-deleted in colorectal cancer signaling acts in a fundamentally different manner, to prevent the Slit2-mediated repulsion of precrossing axons thereby allowing them to approach and cross the midline. These results provide the first evidence for how callosal axons integrate multiple guidance cues to navigate the midline.
['Fothergill|Thomas|T|', 'Donahoo|Amber-Lee S|AL|', 'Douglass|Amelia|A|', 'Zalucki|Oressia|O|', 'Yuan|Jiajia|J|', 'Shu|Tianzhi|T|', 'Goodhill|Geoffrey J|GJ|', 'Richards|Linda J|LJ|']
D000818:Animals D000831:Animals, Newborn D001369:Axons D002478:Cells, Cultured D002540:Cerebral Cortex D018920:Coculture Techniques D003337:Corpus Callosum D000075389:DCC Receptor D004622:Embryo, Mammalian D005260:Female D007839:Functional Laterality D006801:Humans D066298:In Vitro Techniques D036341:Intercellular Signaling Peptides and Proteins D008297:Male D008810:Mice, Inbred C57BL D008818:Mice, Neurologic Mutants D009414:Nerve Growth Factors D009419:Nerve Tissue Proteins D000075388:Netrin-1 D011247:Pregnancy D017208:Rats, Wistar D011956:Receptors, Cell Surface D011971:Receptors, Immunologic D015398:Signal Transduction D025521:Tumor Suppressor Proteins
corpus callosum DCC Robo1 axon guidance commissure formation cortical development neocortex silencing