title: A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation.
abstract: The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. By using mice either with meningeal overgrowth or selective loss of meninges, we have identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonize the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, which is produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development.
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Youngshik
authors.initials: Y
authors.lastname: Choe
authors.forename: Julie A
authors.initials: JA
authors.lastname: Siegenthaler
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Pleasure
mesh_terms: D000367:Age Factors; D061085:Agenesis of Corpus Callosum / Q000235:genetics / Q000473:pathology; D000818:Animals; D001369:Axons / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D055419:Bone Morphogenetic Protein 7 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D003337:Corpus Callosum / Q000196:embryology*; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008578:Meninges / Q000502:physiology*; D051379:Mice; D058953:Neural Stem Cells / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009924:Organ Culture Techniques; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012867:Skin / Q000196:embryology / Q000378:metabolism; D014162:Transfection; D060508:Wnt3 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D055419:Bone Morphogenetic Protein 7; C495267:CTNNB1 protein, mouse; D004791:Enzyme Inhibitors; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; C084119:MSX2 protein; D060508:Wnt3 Protein; D051176:beta Catenin; C525820:bmp7 protein, mouse