title: Frizzled-3a and slit2 genetically interact to modulate midline axon crossing in the telencephalon.
abstract: The anterior commissure forms the first axon connections between the two sides of the embryonic telencephalon. We investigated the role of the transmembrane receptor Frizzled-3a in the development of this commissure using zebrafish as an experimental model. Knock down of Frizzled-3a resulted in complete loss of the anterior commissure. This defect was accompanied by a loss of the glial bridge, expansion of the slit2 expression domain and perturbation of the midline telencephalic-diencephalic boundary. Blocking Slit2 activity following knock down of Frizzled-3a effectively rescued the anterior commissure defect which suggested that Frizzled-3a was indirectly controlling the growth of axons across the rostral midline. We have shown here that Frizzled-3a is essential for normal development of the commissural plate and that loss-of-function causes Slit2-dependent defects in axon midline crossing in the embryonic vertebrate forebrain. These data supports a model whereby Wnt signaling through Frizzled-3a attenuates expression of Slit2 in the rostral midline of the forebrain. The absence of Slit2 facilitates the formation of a midline bridge of glial cells which is used as a substrate for commissural axons. In the absence of this platform of glia, commissural axons fail to cross the rostral midline of the forebrain.
authors.affiliation: School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hofmeister
authors.forename: Christine A
authors.initials: CA
authors.lastname: Devine
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Rothnagel
authors.forename: Brian
authors.initials: B
authors.lastname: Key
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D001483:Base Sequence; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D004027:Diencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005306:Fertilization / Q000187:drug effects; D051157:Frizzled Receptors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D017981:Receptors, Neurotransmitter; D013687:Telencephalon / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D051157:Frizzled Receptors; C498591:Fzd3a protein, zebrafish; D047908:Intracellular Signaling Peptides and Proteins; D060172:Morpholinos; D017981:Receptors, Neurotransmitter; C504432:Slit2 protein, zebrafish; D029961:Zebrafish Proteins