title: Neuronal basic helix-loop-helix proteins Neurod2/6 regulate cortical commissure formation before midline interactions.
abstract: Establishment of long-range fiber tracts by neocortical projection neurons is fundamental for higher brain functions. The molecular control of axon tract formation, however, is still poorly understood. Here, we have identified basic helix-loop-helix (bHLH) transcription factors Neurod2 and Neurod6 as key regulators of fasciculation and targeted axogenesis in the mouse neocortex. In Neurod2/6 double-mutant mice, callosal axons lack expression of the cell adhesion molecule Contactin2, defasciculate in the subventricular zone, and fail to grow toward the midline without forming Probst bundles. Instead, mutant axons overexpress Robo1 and follow random trajectories into the ipsilateral cortex. In contrast to long-range axogenesis, generation and maintenance of pyramidal neurons and initial axon outgrowth are grossly normal, suggesting that these processes are under distinct transcriptional control. Our findings define a new stage in corpus callosum development and demonstrate that neocortical projection neurons require transcriptional specification by neuronal bHLH proteins to execute an intrinsic program of remote connectivity.
authors.affiliation: Max Planck Institute of Experimental Medicine, Department of Neurogenetics, D-37075 Göttingen, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Bormuth
authors.forename: Kuo
authors.initials: K
authors.lastname: Yan
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yonemasu
authors.forename: Maike
authors.initials: M
authors.lastname: Gummert
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zhang
authors.forename: Sven
authors.initials: S
authors.lastname: Wichert
authors.forename: Olga
authors.initials: O
authors.lastname: Grishina
authors.forename: Alexander
authors.initials: A
authors.lastname: Pieper
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zhang
authors.forename: Sandra
authors.initials: S
authors.lastname: Goebbels
authors.forename: Victor
authors.initials: V
authors.lastname: Tarabykin
authors.forename: Klaus-Armin
authors.initials: KA
authors.lastname: Nave
authors.forename: Markus H
authors.initials: MH
authors.lastname: Schwab
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001369:Axons / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology*; D058969:Contactin 2 / Q000235:genetics / Q000502:physiology; D003337:Corpus Callosum / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D018274:Electroporation; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology; D005838:Genotype; D005971:Glutamates / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D061346:Laser Capture Microdissection; D051379:Mice; D009412:Nerve Fibers / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology; D013569:Synapses / Q000502:physiology; D000097905:Roundabout Proteins
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D058969:Contactin 2; D005971:Glutamates; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C548675:Cntn2 protein, mouse; C098995:Neurod2 protein, mouse; C110701:Neurod6 protein, mouse