title: Netrin-DCC signaling regulates corpus callosum formation through attraction of pioneering axons and by modulating Slit2-mediated repulsion.
abstract: 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.
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane, Qld., Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fothergill
authors.forename: Amber-Lee S
authors.initials: AL
authors.lastname: Donahoo
authors.forename: Amelia
authors.initials: A
authors.lastname: Douglass
authors.forename: Oressia
authors.initials: O
authors.lastname: Zalucki
authors.forename: Jiajia
authors.initials: J
authors.lastname: Yuan
authors.forename: Tianzhi
authors.initials: T
authors.lastname: Shu
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Goodhill
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Richards
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques; D003337:Corpus Callosum / Q000502:physiology*; D000075389:DCC Receptor; D004622:Embryo, Mammalian; D005260:Female; D007839:Functional Laterality / Q000235:genetics / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000075388:Netrin-1; D011247:Pregnancy; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D000075389:DCC Receptor; D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075388:Netrin-1; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D025521:Tumor Suppressor Proteins; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C501910:Dcc protein, mouse; C000617351:NTN1 protein, human
keywords: DCC; Robo1; axon guidance; commissure formation; corpus callosum; cortical development; neocortex; silencing