Show simple item record

The secreted metalloprotease ADAMTS20 is required for melanoblast survival.

dc.contributor.author Silver, Debra Lynn
dc.contributor.author Hou, L
dc.contributor.author Somerville, R
dc.contributor.author Young, ME
dc.contributor.author Apte, SS
dc.contributor.author Pavan, WJ
dc.coverage.spatial United States
dc.date.accessioned 2017-04-26T18:19:50Z
dc.date.available 2017-04-26T18:19:50Z
dc.date.issued 2008-02-29
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/18454205
dc.identifier.uri http://hdl.handle.net/10161/14116
dc.description.abstract ADAMTS20 (Adisintegrin-like and metalloprotease domain with thrombospondin type-1 motifs) is a member of a family of secreted metalloproteases that can process a variety of extracellular matrix (ECM) components and secreted molecules. Adamts20 mutations in belted (bt) mice cause white spotting of the dorsal and ventral torso, indicative of defective neural crest (NC)-derived melanoblast development. The expression pattern of Adamts20 in dermal mesenchymal cells adjacent to migrating melanoblasts led us to initially propose that Adamts20 regulated melanoblast migration. However, using a Dct-LacZ transgene to track melanoblast development, we determined that melanoblasts were distributed normally in whole mount E12.5 bt/bt embryos, but were specifically reduced in the trunk of E13.5 bt/bt embryos due to a seven-fold higher rate of apoptosis. The melanoblast defect was exacerbated in newborn skin and embryos from bt/bt animals that were also haploinsufficient for Adamts9, a close homolog of Adamts20, indicating that these metalloproteases functionally overlap in melanoblast development. We identified two potential mechanisms by which Adamts20 may regulate melanoblast survival. First, skin explant cultures demonstrated that Adamts20 was required for melanoblasts to respond to soluble Kit ligand (sKitl). In support of this requirement, bt/bt;Kit(tm1Alf)/+ and bt/bt;Kitl(Sl)/+ mice exhibited synergistically increased spotting. Second, ADAMTS20 cleaved the aggregating proteoglycan versican in vitro and was necessary for versican processing in vivo, raising the possibility that versican can participate in melanoblast development. These findings reveal previously unrecognized roles for Adamts proteases in cell survival and in mediating Kit signaling during melanoblast colonization of the skin. Our results have implications not only for understanding mechanisms of NC-derived melanoblast development but also provide insights on novel biological functions of secreted metalloproteases.
dc.language eng
dc.relation.ispartof PLoS Genet
dc.relation.isversionof 10.1371/journal.pgen.1000003
dc.subject ADAM Proteins
dc.subject ADAMTS Proteins
dc.subject Alleles
dc.subject Animals
dc.subject Base Sequence
dc.subject Cell Differentiation
dc.subject Cell Movement
dc.subject Cell Proliferation
dc.subject Cell Survival
dc.subject DNA Primers
dc.subject Embryonic Stem Cells
dc.subject Female
dc.subject Humans
dc.subject Melanocytes
dc.subject Mice
dc.subject Mice, Inbred C57BL
dc.subject Mice, Mutant Strains
dc.subject Mice, Transgenic
dc.subject Mutation
dc.subject Neural Crest
dc.subject Phenotype
dc.subject Pregnancy
dc.subject Proto-Oncogene Proteins c-kit
dc.subject Signal Transduction
dc.subject Skin
dc.subject Skin Pigmentation
dc.subject Versicans
dc.title The secreted metalloprotease ADAMTS20 is required for melanoblast survival.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/18454205
pubs.begin-page e1000003
pubs.issue 2
pubs.organisational-group Basic Science Departments
pubs.organisational-group Cell Biology
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Institute for Brain Sciences
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Neurobiology
pubs.organisational-group School of Medicine
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published online
pubs.volume 4
dc.identifier.eissn 1553-7404


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record