title: Early Commissural Diencephalic Neurons Control Habenular Axon Extension and Targeting.
abstract: Most neuronal populations form on both the left and right sides of the brain. Their efferent axons appear to grow synchronously along similar pathways on each side, although the neurons or their environment often differ between the two hemispheres [1-4]. How this coordination is controlled has received little attention. Frequently, neurons establish interhemispheric connections, which can function to integrate information between brain hemispheres (e.g., [5]). Such commissures form very early, suggesting their potential developmental role in coordinating ipsilateral axon navigation during embryonic development [4]. To address the temporal-spatial control of bilateral axon growth, we applied long-term time-lapse imaging to visualize the formation of the conserved left-right asymmetric habenular neural circuit in the developing zebrafish embryo [6]. Although habenular neurons are born at different times across brain hemispheres [7], we found that elongation of habenular axons occurs synchronously. The initiation of axon extension is not controlled within the habenular network itself but through an early developing proximal diencephalic network. The commissural neurons of this network influence habenular axons both ipsilaterally and contralaterally. Their unilateral absence impairs commissure formation and coordinated habenular axon elongation and causes their subsequent arrest on both sides of the brain. Thus, habenular neural circuit formation depends on a second intersecting commissural network, which facilitates the exchange of information between hemispheres required for ipsilaterally projecting habenular axons. This mechanism of network formation may well apply to other circuits, and has only remained undiscovered due to technical limitations.
authors.affiliation: Department of Cell and Molecular Biology, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Strasse 13-17, 68167 Mannheim, Germany; Nikon Imaging Center, Heidelberg University, Bioquant, 69120 Heidelberg, Germany; Cluster of Excellence CellNetworks, Heidelberg University, Bioquant, 69120 Heidelberg, Germany.
authors.forename: Carlo A
authors.initials: CA
authors.lastname: Beretta
authors.affiliation: Nikon Imaging Center, Heidelberg University, Bioquant, 69120 Heidelberg, Germany; Cluster of Excellence CellNetworks, Heidelberg University, Bioquant, 69120 Heidelberg, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dross
authors.affiliation: Department of Cell and Molecular Biology, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Strasse 13-17, 68167 Mannheim, Germany.
authors.forename: Luca
authors.initials: L
authors.lastname: Guglielmi
authors.affiliation: Nikon Imaging Center, Heidelberg University, Bioquant, 69120 Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bankhead
authors.affiliation: Institut de Biologie, Ecole Normale Superieure, IBENS, 75005 Paris, France; INSERM U1024, 75005 Paris, France; CNRS UMR8197, 75005 Paris, France.
authors.forename: Marina
authors.initials: M
authors.lastname: Soulika
authors.affiliation: Developmental Genetics of the Nervous System, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany; Centre for Organismal Studies, Heidelberg University, 69120 Heidelberg, Germany.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Gutierrez-Triana
authors.affiliation: Department of Cell and Molecular Biology, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Strasse 13-17, 68167 Mannheim, Germany; Centre for Organismal Studies, Heidelberg University, 69120 Heidelberg, Germany.
authors.forename: Alessio
authors.initials: A
authors.lastname: Paolini
authors.affiliation: Centre for Organismal Studies, Heidelberg University, 69120 Heidelberg, Germany; The David J. Apple Center for Vision Research, Heidelberg University, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
authors.forename: Lucia
authors.initials: L
authors.lastname: Poggi
authors.affiliation: INMG-UMR5310-INSERM U1217, University of Lyon, Université Claude Bernard Lyon 1, 69622 Villeurbanne, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Falk
authors.affiliation: Developmental Genetics of the Nervous System, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany; Focus Program Translational Neuroscience, University Medical Center, Johannes Gutenberg University, Langenbeckstrasse 1, 55131 Mainz, Germany.
authors.forename: Soojin
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Institut de Biologie, Ecole Normale Superieure, IBENS, 75005 Paris, France; INSERM U1024, 75005 Paris, France; CNRS UMR8197, 75005 Paris, France.
authors.forename: Marika
authors.initials: M
authors.lastname: Kapsimali
authors.affiliation: Nikon Imaging Center, Heidelberg University, Bioquant, 69120 Heidelberg, Germany; Cluster of Excellence CellNetworks, Heidelberg University, Bioquant, 69120 Heidelberg, Germany; Centre for Organismal Studies, Heidelberg University, 69120 Heidelberg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Engel
authors.affiliation: Department of Cell and Molecular Biology, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Strasse 13-17, 68167 Mannheim, Germany. Electronic address: matthias.carl@medma.uni-heidelberg.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Carl
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D019521:Body Patterning; D004027:Diencephalon / Q000166:cytology / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D059008:Time-Lapse Imaging; D015027:Zebrafish / Q000254:growth & development / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D029961:Zebrafish Proteins
keywords: asymmetry; axon elongation; brain; commissures; habenula; neural network; thalamus; time lapse; zebrafish