title: Neuroblast migration along the anteroposterior axis of C. elegans is controlled by opposing gradients of Wnts and a secreted Frizzled-related protein.
abstract: The migration of neuroblasts along the anteroposterior body axis of C. elegans is controlled by multiple Wnts that act partially redundantly to guide cells to their precisely defined final destinations. How positional information is specified by this system is, however, still largely unknown. Here, we used a novel fluorescent in situ hybridization methods to generate a quantitative spatiotemporal expression map of the C. elegans Wnt genes. We found that the five Wnt genes are expressed in a series of partially overlapping domains along the anteroposterior axis, with a predominant expression in the posterior half of the body. Furthermore, we show that a secreted Frizzled-related protein is expressed at the anterior end of the body axis, where it inhibits Wnt signaling to control neuroblast migration. Our findings reveal that a system of regionalized Wnt gene expression and anterior Wnt inhibition guides the highly stereotypic migration of neuroblasts in C. elegans. Opposing expression of Wnts and Wnt inhibitors has been observed in basal metazoans and in the vertebrate neurectoderm. Our results in C. elegans support the notion that a system of posterior Wnt signaling and anterior Wnt inhibition is an evolutionarily conserved principle of primary body axis specification.
authors.affiliation: Hubrecht Institute, Royal Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, Utrecht, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Harterink
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Teije C
authors.initials: TC
authors.lastname: Middelkoop
authors.forename: Thang Dinh
authors.initials: TD
authors.lastname: Doan
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
authors.forename: Hendrik C
authors.initials: HC
authors.lastname: Korswagen
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000196:embryology*; D002465:Cell Movement / Q000502:physiology*; D003001:Cloning, Molecular; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*; D000099274:Frizzled-Related Proteins
chemical_list: D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D000099274:Frizzled-Related Proteins