title: Netrins and Wnts function redundantly to regulate antero-posterior and dorso-ventral guidance in C. elegans.
abstract: Guided migrations of cells and developing axons along the dorso-ventral (D/V) and antero-posterior (A/P) body axes govern tissue patterning and neuronal connections. In C. elegans, as in vertebrates, D/V and A/P graded distributions of UNC-6/Netrin and Wnts, respectively, provide instructive polarity information to guide cells and axons migrating along these axes. By means of a comprehensive genetic analysis, we found that simultaneous loss of Wnt and Netrin signaling components reveals previously unknown and unexpected redundant roles for Wnt and Netrin signaling pathways in both D/V and A/P guidance of migrating cells and axons in C. elegans, as well as in processes essential for organ function and viability. Thus, in addition to providing polarity information for migration along the axis of their gradation, Wnts and Netrin are each able to guide migrations orthogonal to the axis of their gradation. Netrin signaling not only functions redundantly with some Wnts, but also counterbalances the effects of others to guide A/P migrations, while the involvement of Wnt signaling in D/V guidance identifies Wnt signaling as one of the long sought mechanisms that functions in parallel to Netrin signaling to promote D/V guidance of cells and axons. These findings provide new avenues for deciphering how A/P and D/V guidance signals are integrated within the cell to establish polarity in multiple biological processes, and implicate broader roles for Netrin and Wnt signaling--roles that are currently masked due to prevalent redundancy.
authors.affiliation: Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Naomi
authors.initials: N
authors.lastname: Levy-Strumpf
authors.affiliation: Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Culotti
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D000075385:Netrins; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; D000075385:Netrins; D011956:Receptors, Cell Surface; C078146:UNC-6 protein, C elegans; D051153:Wnt Proteins; C077588:UNC-5 protein, C elegans