title: Chemoattractant axon guidance cues regulate de novo axon trajectories in the embryonic forebrain of zebrafish.
abstract: The development of axon tracts in the early vertebrate brain is controlled by combinations of soluble, membrane-bound and extracellular matrix molecules. How these multiple and sometimes conflicting guidance cues are integrated in order to establish stereotypical pathways remains to be determined. We show here that when interactions between the chemoattractive signal Netrin1a and its receptor Dcc are suppressed using a loss-of-function approach, a novel axon trajectory emerges in the dorsal diencephalon. Axons arising from a subpopulation of telencephalic neurons failed to project rostrally into the anterior commissure in the absence of either Netrin1a or Dcc. Instead these axons inappropriately exited the telencephalon and ectopically coursed caudally into virgin neuroepithelium. This response was highly specific since loss-of-function of Netrin1b, a paralogue of Netrin1a, generated a distinct phenotype in the rostral brain. These results show that a subpopulation of telencephalic neurons, when freed from long-range chemoattraction mediated by Netrin1a-Dcc interactions, follow alternative instructive cues that lead to creation of an ectopic axon bundle in the diencephalon. This work provides insight into how integration of multiple guidance signals defines the initial scaffold of axon tracts in the embryonic vertebrate forebrain.
authors.affiliation: Brain Growth and Regeneration Lab, School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Queensland, Australia. a.gaudin@uq.edu.au
authors.forename: Arnaud
authors.initials: A
authors.lastname: Gaudin
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hofmeister
authors.forename: Brian
authors.initials: B
authors.lastname: Key
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism*; D001483:Base Sequence; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism; D000075389:DCC Receptor; D016373:DNA, Antisense / Q000235:genetics; D004027:Diencephalon / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D009414:Nerve Growth Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000075388:Netrin-1; D009434:Neural Pathways / Q000196:embryology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D016548:Prosencephalon / Q000196:embryology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002630:Chemotactic Factors; D000075389:DCC Receptor; D016373:DNA, Antisense; D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins; C506552:dcc protein, zebrafish; D000075388:Netrin-1