title: The Caenorhabditis elegans homolog of the Opitz syndrome gene, madd-2/Mid1, regulates anchor cell invasion during vulval development.
abstract: Mutations in the human Mid1 gene cause Opitz G/BBB syndrome, which is characterized by various midline closure defects. The Caenorhabditis elegans homolog of Mid1, madd-2, positively regulates signaling by the unc-40 Netrin receptor during the extension of muscle arms to the midline and in axon guidance and branching. During uterine development, a specialized cell called anchor cell (AC) breaches the basal laminae separating the uterus from the epidermis and invades the underlying vulval tissue. AC invasion is guided by an UNC-6 Netrin signal from the ventral nerve cord and an unknown guidance signal from the vulval cells. Using genetic epistasis analysis, we show that madd-2 regulates AC invasion downstream of or in parallel with the Netrin signaling pathway. Measurements of AC shape, polarity and dynamics indicate that MADD-2 prevents the formation of ectopic AC protrusions in the absence of guidance signals. We propose that MADD-2 represses the intrinsic invasive capacity of the AC, while the Netrin and vulval guidance cues locally overcome this inhibitory activity of MADD-2 to guide the AC ventrally into the vulval tissue. Therefore, developmental cell invasion depends on a precise balance between pro- and anti-invasive factors.
authors.affiliation: Institute of Molecular Life Sciences, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors.forename: Matthias K
authors.initials: MK
authors.lastname: Morf
authors.forename: Ivo
authors.initials: I
authors.lastname: Rimann
authors.forename: Mariam
authors.initials: M
authors.lastname: Alexander
authors.forename: Peter
authors.initials: P
authors.lastname: Roy
authors.forename: Alex
authors.initials: A
authors.lastname: Hajnal
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D002972:Cleft Palate / Q000235:genetics*; D004947:Esophagus / Q000002:abnormalities / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D006972:Hypertelorism / Q000235:genetics*; D007021:Hypospadias / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008868:Microtubule Proteins / Q000502:physiology; D008954:Models, Biological; D009687:Nuclear Proteins / Q000502:physiology; D034622:RNA Interference; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D044767:Ubiquitin-Protein Ligases; D014844:Vulva / Q000196:embryology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D008868:Microtubule Proteins; D009687:Nuclear Proteins; C551653:TRIM-9 protein, C elegans; D014157:Transcription Factors; C102174:UNC-40 protein, C elegans; C109052:MID1 protein, human; D044767:Ubiquitin-Protein Ligases