ADAMTS Metalloproteases Generate Active Versican Fragments that Regulate Interdigital Web Regression
We show that combinatorial mouse alleles for the secreted metalloproteases Adamts5, Adamts20 ( bt), and Adamts9 result in fully penetrant soft-tissue syndactyly. Interdigital webs in Adamts5 −/−;bt/bt mice had reduced apoptosis and decreased cleavage of the proteoglycan versican; however, the BMP-FG...
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| Veröffentlicht in: | Developmental cell 2009-11, Vol.17 (5), p.687-698 |
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| creator | McCulloch, Daniel R. Nelson, Courtney M. Dixon, Laura J. Silver, Debra L. Wylie, James D. Lindner, Volkhard Sasaki, Takako Cooley, Marion A. Argraves, W. Scott Apte, Suneel S. |
| description | We show that combinatorial mouse alleles for the secreted metalloproteases
Adamts5,
Adamts20 (
bt), and
Adamts9 result in fully penetrant soft-tissue syndactyly. Interdigital webs in
Adamts5
−/−;bt/bt
mice had reduced apoptosis and decreased cleavage of the proteoglycan versican; however, the BMP-FGF axis, which regulates interdigital apoptosis was unaffected. BMP4 induced apoptosis, but without concomitant versican proteolysis. Haploinsufficiency of either
Vcan or
Fbln1, a cofactor for versican processing by ADAMTS5, led to highly penetrant syndactyly in
bt mice, suggesting that cleaved versican was essential for web regression. The local application of an aminoterminal versican fragment corresponding to ADAMTS-processed versican, induced cell death in
Adamts5
−/−;bt/bt
webs. Thus, ADAMTS proteases cooperatively maintain versican proteolysis above a required threshold to create a permissive environment for apoptosis. The data highlight the developmental significance of proteolytic action on the ECM, not only as a clearance mechanism, but also as a means to generate bioactive versican fragments. |
| doi_str_mv | 10.1016/j.devcel.2009.09.008 |
| format | Article |
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Adamts5,
Adamts20 (
bt), and
Adamts9 result in fully penetrant soft-tissue syndactyly. Interdigital webs in
Adamts5
−/−;bt/bt
mice had reduced apoptosis and decreased cleavage of the proteoglycan versican; however, the BMP-FGF axis, which regulates interdigital apoptosis was unaffected. BMP4 induced apoptosis, but without concomitant versican proteolysis. Haploinsufficiency of either
Vcan or
Fbln1, a cofactor for versican processing by ADAMTS5, led to highly penetrant syndactyly in
bt mice, suggesting that cleaved versican was essential for web regression. The local application of an aminoterminal versican fragment corresponding to ADAMTS-processed versican, induced cell death in
Adamts5
−/−;bt/bt
webs. Thus, ADAMTS proteases cooperatively maintain versican proteolysis above a required threshold to create a permissive environment for apoptosis. The data highlight the developmental significance of proteolytic action on the ECM, not only as a clearance mechanism, but also as a means to generate bioactive versican fragments.</description><identifier>ISSN: 1534-5807</identifier><identifier>EISSN: 1878-1551</identifier><identifier>DOI: 10.1016/j.devcel.2009.09.008</identifier><identifier>PMID: 19922873</identifier><language>eng</language><publisher>Cambridge, MA: Elsevier Inc</publisher><subject>ADAM Proteins - deficiency ; ADAM Proteins - genetics ; ADAM Proteins - metabolism ; ADAMTS Proteins ; ADAMTS5 Protein ; ADAMTS9 Protein ; Animals ; Apoptosis ; Biological and medical sciences ; Body Patterning ; Calcium-Binding Proteins - metabolism ; Cell differentiation, maturation, development, hematopoiesis ; Cell physiology ; CELLCYCLE ; DEVBIO ; Extremities - embryology ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Enzymologic ; Mice ; Mice, Knockout ; Molecular and cellular biology ; SIGNALING ; Versicans - metabolism</subject><ispartof>Developmental cell, 2009-11, Vol.17 (5), p.687-698</ispartof><rights>2009 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>2009 Elsevier Inc. All rights reserved. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c492t-fb03366ebda49ac3e802d812f3823b11295b7a592b1d1907f7df808f4fe590e53</citedby><cites>FETCH-LOGICAL-c492t-fb03366ebda49ac3e802d812f3823b11295b7a592b1d1907f7df808f4fe590e53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.devcel.2009.09.008$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22174766$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19922873$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McCulloch, Daniel R.</creatorcontrib><creatorcontrib>Nelson, Courtney M.</creatorcontrib><creatorcontrib>Dixon, Laura J.</creatorcontrib><creatorcontrib>Silver, Debra L.</creatorcontrib><creatorcontrib>Wylie, James D.</creatorcontrib><creatorcontrib>Lindner, Volkhard</creatorcontrib><creatorcontrib>Sasaki, Takako</creatorcontrib><creatorcontrib>Cooley, Marion A.</creatorcontrib><creatorcontrib>Argraves, W. Scott</creatorcontrib><creatorcontrib>Apte, Suneel S.</creatorcontrib><title>ADAMTS Metalloproteases Generate Active Versican Fragments that Regulate Interdigital Web Regression</title><title>Developmental cell</title><addtitle>Dev Cell</addtitle><description>We show that combinatorial mouse alleles for the secreted metalloproteases
Adamts5,
Adamts20 (
bt), and
Adamts9 result in fully penetrant soft-tissue syndactyly. Interdigital webs in
Adamts5
−/−;bt/bt
mice had reduced apoptosis and decreased cleavage of the proteoglycan versican; however, the BMP-FGF axis, which regulates interdigital apoptosis was unaffected. BMP4 induced apoptosis, but without concomitant versican proteolysis. Haploinsufficiency of either
Vcan or
Fbln1, a cofactor for versican processing by ADAMTS5, led to highly penetrant syndactyly in
bt mice, suggesting that cleaved versican was essential for web regression. The local application of an aminoterminal versican fragment corresponding to ADAMTS-processed versican, induced cell death in
Adamts5
−/−;bt/bt
webs. Thus, ADAMTS proteases cooperatively maintain versican proteolysis above a required threshold to create a permissive environment for apoptosis. The data highlight the developmental significance of proteolytic action on the ECM, not only as a clearance mechanism, but also as a means to generate bioactive versican fragments.</description><subject>ADAM Proteins - deficiency</subject><subject>ADAM Proteins - genetics</subject><subject>ADAM Proteins - metabolism</subject><subject>ADAMTS Proteins</subject><subject>ADAMTS5 Protein</subject><subject>ADAMTS9 Protein</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Body Patterning</subject><subject>Calcium-Binding Proteins - metabolism</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell physiology</subject><subject>CELLCYCLE</subject><subject>DEVBIO</subject><subject>Extremities - embryology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Molecular and cellular biology</subject><subject>SIGNALING</subject><subject>Versicans - metabolism</subject><issn>1534-5807</issn><issn>1878-1551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV9rFDEUxYMotla_gci8iE-z5t9MkhdhqbYWWgSt-hgyyc02y2xmm2QX_PZm3KXVF-FCAvd3T07uQeg1wQuCSf9-vXCwtzAuKMZqMReWT9ApkUK2pOvI03rvGG87icUJepHzGtcxIvFzdEKUolQKdorc8uPy5vZbcwPFjOO0TVMBkyE3lxAhmQLN0pawh-YHpBysic1FMqsNxJKbcmdK8xVWu3HmrmKB5MIqVKHmJwxzJ0HOYYov0TNvxgyvjucZ-n7x6fb8c3v95fLqfHndWq5oaf2AGet7GJzhylgGElMnCfVMUjYQQlU3CNMpOhBHFBZeOC-x9NxDpzB07Ax9OOhud8MGnK0ukxn1NoWNSb_0ZIL-txPDnV5Ne02FxJzTKvDuKJCm-x3kojch1x2PJsK0y1owTrgQWFaSH0ibppwT-IdXCNZzPnqtD_noOR8915-xN387fBw6BlKBt0fAZGtGn0y0IT9wlBLBRd8_fhXqPvcBks42QLTgQgJbtJvC_538BqEFsgw</recordid><startdate>20091117</startdate><enddate>20091117</enddate><creator>McCulloch, Daniel R.</creator><creator>Nelson, Courtney M.</creator><creator>Dixon, Laura J.</creator><creator>Silver, Debra L.</creator><creator>Wylie, James D.</creator><creator>Lindner, Volkhard</creator><creator>Sasaki, Takako</creator><creator>Cooley, Marion A.</creator><creator>Argraves, W. Scott</creator><creator>Apte, Suneel S.</creator><general>Elsevier Inc</general><general>Cell Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20091117</creationdate><title>ADAMTS Metalloproteases Generate Active Versican Fragments that Regulate Interdigital Web Regression</title><author>McCulloch, Daniel R. ; Nelson, Courtney M. ; Dixon, Laura J. ; Silver, Debra L. ; Wylie, James D. ; Lindner, Volkhard ; Sasaki, Takako ; Cooley, Marion A. ; Argraves, W. Scott ; Apte, Suneel S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-fb03366ebda49ac3e802d812f3823b11295b7a592b1d1907f7df808f4fe590e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>ADAM Proteins - deficiency</topic><topic>ADAM Proteins - genetics</topic><topic>ADAM Proteins - metabolism</topic><topic>ADAMTS Proteins</topic><topic>ADAMTS5 Protein</topic><topic>ADAMTS9 Protein</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Body Patterning</topic><topic>Calcium-Binding Proteins - metabolism</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell physiology</topic><topic>CELLCYCLE</topic><topic>DEVBIO</topic><topic>Extremities - embryology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Molecular and cellular biology</topic><topic>SIGNALING</topic><topic>Versicans - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McCulloch, Daniel R.</creatorcontrib><creatorcontrib>Nelson, Courtney M.</creatorcontrib><creatorcontrib>Dixon, Laura J.</creatorcontrib><creatorcontrib>Silver, Debra L.</creatorcontrib><creatorcontrib>Wylie, James D.</creatorcontrib><creatorcontrib>Lindner, Volkhard</creatorcontrib><creatorcontrib>Sasaki, Takako</creatorcontrib><creatorcontrib>Cooley, Marion A.</creatorcontrib><creatorcontrib>Argraves, W. Scott</creatorcontrib><creatorcontrib>Apte, Suneel S.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Developmental cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McCulloch, Daniel R.</au><au>Nelson, Courtney M.</au><au>Dixon, Laura J.</au><au>Silver, Debra L.</au><au>Wylie, James D.</au><au>Lindner, Volkhard</au><au>Sasaki, Takako</au><au>Cooley, Marion A.</au><au>Argraves, W. Scott</au><au>Apte, Suneel S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ADAMTS Metalloproteases Generate Active Versican Fragments that Regulate Interdigital Web Regression</atitle><jtitle>Developmental cell</jtitle><addtitle>Dev Cell</addtitle><date>2009-11-17</date><risdate>2009</risdate><volume>17</volume><issue>5</issue><spage>687</spage><epage>698</epage><pages>687-698</pages><issn>1534-5807</issn><eissn>1878-1551</eissn><abstract>We show that combinatorial mouse alleles for the secreted metalloproteases
Adamts5,
Adamts20 (
bt), and
Adamts9 result in fully penetrant soft-tissue syndactyly. Interdigital webs in
Adamts5
−/−;bt/bt
mice had reduced apoptosis and decreased cleavage of the proteoglycan versican; however, the BMP-FGF axis, which regulates interdigital apoptosis was unaffected. BMP4 induced apoptosis, but without concomitant versican proteolysis. Haploinsufficiency of either
Vcan or
Fbln1, a cofactor for versican processing by ADAMTS5, led to highly penetrant syndactyly in
bt mice, suggesting that cleaved versican was essential for web regression. The local application of an aminoterminal versican fragment corresponding to ADAMTS-processed versican, induced cell death in
Adamts5
−/−;bt/bt
webs. Thus, ADAMTS proteases cooperatively maintain versican proteolysis above a required threshold to create a permissive environment for apoptosis. The data highlight the developmental significance of proteolytic action on the ECM, not only as a clearance mechanism, but also as a means to generate bioactive versican fragments.</abstract><cop>Cambridge, MA</cop><pub>Elsevier Inc</pub><pmid>19922873</pmid><doi>10.1016/j.devcel.2009.09.008</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Developmental cell, 2009-11, Vol.17 (5), p.687-698 |
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| source | MEDLINE; Cell Press Free Archives; Access via ScienceDirect (Elsevier); EZB-FREE-00999 freely available EZB journals |
| subjects | ADAM Proteins - deficiency ADAM Proteins - genetics ADAM Proteins - metabolism ADAMTS Proteins ADAMTS5 Protein ADAMTS9 Protein Animals Apoptosis Biological and medical sciences Body Patterning Calcium-Binding Proteins - metabolism Cell differentiation, maturation, development, hematopoiesis Cell physiology CELLCYCLE DEVBIO Extremities - embryology Fundamental and applied biological sciences. Psychology Gene Expression Regulation, Developmental Gene Expression Regulation, Enzymologic Mice Mice, Knockout Molecular and cellular biology SIGNALING Versicans - metabolism |
| title | ADAMTS Metalloproteases Generate Active Versican Fragments that Regulate Interdigital Web Regression |
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