title: Xenopus ADAM19 is involved in neural, neural crest and muscle development.
abstract: ADAM19 is a member of the meltrin subfamily of ADAM metalloproteases. In Xenopus, ADAM19 is present as a maternal transcript. Zygotic expression starts during gastrulation and is apparent in the dorsal blastopore lip. ADAM19 expression through neurulation and tailbud formation becomes enriched in dorsal structures such as the neural tube, the notochord and the somites. Using morpholino knock-down, we show that a reduction of ADAM19 protein in gastrula stage embryos results in a decrease of Brachyury expression in the notochord concomitant with an increase in the dorsal markers, Goosecoid and Chordin. These changes in gene expression are accompanied by a decrease in phosphorylated AKT, a downstream target of the EGF signaling pathway, and occur while the blastopore closes at the same rate as the control embryos. During neurulation and tailbud formation, ADAM19 knock-down induces a reduction of the neural markers N-tubulin and NRP1 but not Sox2. In the somitic mesoderm, the expression of MLC is also decreased while MyoD is not. ADAM19 knockdown also reduces neural crest markers prior to cell migration. Neural crest induction is also decreased in embryos treated with an EGF receptor inhibitor suggesting that this pathway is necessary for neural crest cell induction. Using targeted knock-down of ADAM19 we show that the reduction of neural and neural crest markers is cell autonomous and that the migration if the cranial neural crest is perturbed. We further show that ADAM19 protein reduction affects somite organization, reduces 12-101 expression and perturbs fibronectin localization at the intersomitic boundary.
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts, Paige Laboratory, Room 203, 161 Holdsworth Way, Amherst 01003, USA.
authors.forename: Russell
authors.initials: R
authors.lastname: Neuner
authors.forename: Hélène
authors.initials: H
authors.lastname: Cousin
authors.forename: Catherine
authors.initials: C
authors.lastname: McCusker
authors.forename: Michael
authors.initials: M
authors.lastname: Coyne
authors.forename: Dominique
authors.initials: D
authors.lastname: Alfandari
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019521:Body Patterning / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D005326:Fetal Proteins / Q000378:metabolism; D005775:Gastrula / Q000187:drug effects / Q000196:embryology / Q000201:enzymology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008648:Mesoderm / Q000187:drug effects / Q000196:embryology; D024510:Muscle Development / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology*; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology*; D054259:Neural Tube / Q000187:drug effects / Q000196:embryology / Q000201:enzymology; D009672:Notochord / Q000187:drug effects / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019170:Somites / Q000187:drug effects / Q000196:embryology / Q000201:enzymology; D020825:T-Box Domain Proteins / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics; D015053:Zygote / Q000187:drug effects / Q000201:enzymology; D000098908:Brachyury Protein
chemical_list: D051722:ADAM Proteins; D015415:Biomarkers; D004815:Epidermal Growth Factor; D005326:Fetal Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D029867:Xenopus Proteins; D000098908:Brachyury Protein; C539706:ADAM19 protein, Xenopus