Multi-Layered hypertrophied MEE formation by microtubule disruption via GEF-H1/RhoA/ROCK signaling pathway
Background: Formation of the secondary palate is complex and disturbance during palatal fusion may result in cleft palate. The processes of adhesion, intercalation, and disappearance of medial edge epithelia (MEE) are characterized by morphological changes requiring dynamic cytoskeletal rearrangemen...
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| Veröffentlicht in: | Developmental dynamics 2012-07, Vol.241 (7), p.1169-1182 |
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| creator | Kitase, Yukiko Shuler, Charles F. |
| description | Background: Formation of the secondary palate is complex and disturbance during palatal fusion may result in cleft palate. The processes of adhesion, intercalation, and disappearance of medial edge epithelia (MEE) are characterized by morphological changes requiring dynamic cytoskeletal rearrangement. Microtubules are one of the cytoskeletal elements involved in maintenance of cell morphology. Microtubule‐disrupting drugs have been reported to cause craniofacial malformations including cleft palate. The mechanisms underlying the failure of palatal fusion remain poorly understood. We evaluated the effect of nocodazole (NDZ), a drug that disrupts microtubules, on palatal fusion in organ culture. Results: NDZ caused failure of palatal fusion due to the induction of a multi‐layered hypertrophied MEE in the mid‐region of the secondary palatal shelves. Microtubule disruption increased RhoA activity and stress fiber formation. Pharmacological inhibition of the RhoA/ROCK pathway blocked multi‐layered MEE formation. Partial prevention of hypertrophied MEE was observed with Y27632 and cytochalasin, but not with blebbistatin. NDZ induced re‐localization of GEF‐H1 into cytoplasm from cell–cell junctions. Conclusions: The present study provided evidence that the GEF‐H1/RhoA/ROCK pathway plays a pivotal role in linking microtubule disassembly to the remodeling of the actin cytoskeleton, which resulted in a multi‐layered hypertrophied MEE and failure of palatal fusion. Developmental Dynamics 241:1169–1182, 2012. © 2012 Wiley Periodicals, Inc.
Key findings:
Microtubule disassembly causes failure of palatal fusion due to multi‐layered hypertrophied MEE formation in the middle region of the palatal shelves.
Nocodazole activates RhoA/ROCK signaling pathway and stress fiber formation in MEE
Multi‐layered hypertrophied MEE formation is not dependent on TGF‐β/Smad signaling.
GEF‐H1/RhoA/ROCK signaling pathway is involved in multi‐layred hypertrophied MEE formation. |
| doi_str_mv | 10.1002/dvdy.23800 |
| format | Article |
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Key findings:
Microtubule disassembly causes failure of palatal fusion due to multi‐layered hypertrophied MEE formation in the middle region of the palatal shelves.
Nocodazole activates RhoA/ROCK signaling pathway and stress fiber formation in MEE
Multi‐layered hypertrophied MEE formation is not dependent on TGF‐β/Smad signaling.
GEF‐H1/RhoA/ROCK signaling pathway is involved in multi‐layred hypertrophied MEE formation.</description><identifier>ISSN: 1058-8388</identifier><identifier>EISSN: 1097-0177</identifier><identifier>DOI: 10.1002/dvdy.23800</identifier><identifier>PMID: 22565548</identifier><language>eng</language><publisher>New York: Wiley-Liss, Inc</publisher><subject>Animals ; Blotting, Western ; Cell Proliferation - drug effects ; Female ; Fluorescent Antibody Technique ; GEF-H1/RhoA/ROCK ; Guanine Nucleotide Exchange Factors ; Hypertrophy ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; microtubule ; Microtubules - drug effects ; Microtubules - metabolism ; multi-layered hypertrophied MEE ; Nocodazole - pharmacology ; Organ Culture Techniques ; palatal fusion ; Palate - drug effects ; Palate - embryology ; Palate - metabolism ; Pregnancy ; Proto-Oncogene Proteins ; Real-Time Polymerase Chain Reaction ; Rho Guanine Nucleotide Exchange Factors ; rhoA GTP-Binding Protein - genetics ; rhoA GTP-Binding Protein - metabolism ; Signal Transduction - drug effects ; Transforming Growth Factor beta - genetics ; Transforming Growth Factor beta - metabolism</subject><ispartof>Developmental dynamics, 2012-07, Vol.241 (7), p.1169-1182</ispartof><rights>Copyright © 2012 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4970-1a0b7a9787243fbb7098a8acb5378bd55d0c57bed14415fe2f9b202db4ca24d23</citedby><cites>FETCH-LOGICAL-c4970-1a0b7a9787243fbb7098a8acb5378bd55d0c57bed14415fe2f9b202db4ca24d23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fdvdy.23800$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fdvdy.23800$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22565548$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kitase, Yukiko</creatorcontrib><creatorcontrib>Shuler, Charles F.</creatorcontrib><title>Multi-Layered hypertrophied MEE formation by microtubule disruption via GEF-H1/RhoA/ROCK signaling pathway</title><title>Developmental dynamics</title><addtitle>Dev. Dyn</addtitle><description>Background: Formation of the secondary palate is complex and disturbance during palatal fusion may result in cleft palate. The processes of adhesion, intercalation, and disappearance of medial edge epithelia (MEE) are characterized by morphological changes requiring dynamic cytoskeletal rearrangement. Microtubules are one of the cytoskeletal elements involved in maintenance of cell morphology. Microtubule‐disrupting drugs have been reported to cause craniofacial malformations including cleft palate. The mechanisms underlying the failure of palatal fusion remain poorly understood. We evaluated the effect of nocodazole (NDZ), a drug that disrupts microtubules, on palatal fusion in organ culture. Results: NDZ caused failure of palatal fusion due to the induction of a multi‐layered hypertrophied MEE in the mid‐region of the secondary palatal shelves. Microtubule disruption increased RhoA activity and stress fiber formation. Pharmacological inhibition of the RhoA/ROCK pathway blocked multi‐layered MEE formation. Partial prevention of hypertrophied MEE was observed with Y27632 and cytochalasin, but not with blebbistatin. NDZ induced re‐localization of GEF‐H1 into cytoplasm from cell–cell junctions. Conclusions: The present study provided evidence that the GEF‐H1/RhoA/ROCK pathway plays a pivotal role in linking microtubule disassembly to the remodeling of the actin cytoskeleton, which resulted in a multi‐layered hypertrophied MEE and failure of palatal fusion. Developmental Dynamics 241:1169–1182, 2012. © 2012 Wiley Periodicals, Inc.
Key findings:
Microtubule disassembly causes failure of palatal fusion due to multi‐layered hypertrophied MEE formation in the middle region of the palatal shelves.
Nocodazole activates RhoA/ROCK signaling pathway and stress fiber formation in MEE
Multi‐layered hypertrophied MEE formation is not dependent on TGF‐β/Smad signaling.
GEF‐H1/RhoA/ROCK signaling pathway is involved in multi‐layred hypertrophied MEE formation.</description><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cell Proliferation - drug effects</subject><subject>Female</subject><subject>Fluorescent Antibody Technique</subject><subject>GEF-H1/RhoA/ROCK</subject><subject>Guanine Nucleotide Exchange Factors</subject><subject>Hypertrophy</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>microtubule</subject><subject>Microtubules - drug effects</subject><subject>Microtubules - metabolism</subject><subject>multi-layered hypertrophied MEE</subject><subject>Nocodazole - pharmacology</subject><subject>Organ Culture Techniques</subject><subject>palatal fusion</subject><subject>Palate - drug effects</subject><subject>Palate - embryology</subject><subject>Palate - metabolism</subject><subject>Pregnancy</subject><subject>Proto-Oncogene Proteins</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Rho Guanine Nucleotide Exchange Factors</subject><subject>rhoA GTP-Binding Protein - genetics</subject><subject>rhoA GTP-Binding Protein - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Transforming Growth Factor beta - genetics</subject><subject>Transforming Growth Factor beta - metabolism</subject><issn>1058-8388</issn><issn>1097-0177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtP3DAURq0KVCjtpj-gisSmqhTGz9hZonkiBqhQW9SVZccO4yGZpHYC5N_jYYAFi658LZ97dH0_AL4ieIIgxCNzb4YTTASEH8AhgjlPIeJ8b1szkQoixAH4FMIaQigyij6CA4xZxhgVh2B90VedS5dqsN6aZDW01ne-aVcu3i6m06RsfK0612wSPSS1K3zT9bqvbGJc8H37_HLvVDKfztIFGl2vmtPR9dX4PAnudqMqt7lNWtWtHtTwGeyXqgr2y8t5BH7Ppr_Gi3R5NT8bny7TguYcpkhBzVXOBceUlFpzmAslVKEZ4UIbxgwsGNfWIEoRKy0uc40hNpoWClODyRH4vvO2vvnX29DJ2oXCVpXa2KYPEkEMBRY4zyN6_A5dN72PY0eKZ5lAFBESqR87Kn4-BG9L2XpXKz9EldwmILcJyOcEIvztRdnr2po39HXlEUA74MFVdviPSk7-TP6-StNdjwudfXzrUf5OZpxwJm8u5_InY2KSLW7kjDwBe2-fWA</recordid><startdate>201207</startdate><enddate>201207</enddate><creator>Kitase, Yukiko</creator><creator>Shuler, Charles F.</creator><general>Wiley-Liss, Inc</general><general>Wiley‐Liss, Inc</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7SS</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>JQ2</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201207</creationdate><title>Multi-Layered hypertrophied MEE formation by microtubule disruption via GEF-H1/RhoA/ROCK signaling pathway</title><author>Kitase, Yukiko ; Shuler, Charles F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4970-1a0b7a9787243fbb7098a8acb5378bd55d0c57bed14415fe2f9b202db4ca24d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cell Proliferation - drug effects</topic><topic>Female</topic><topic>Fluorescent Antibody Technique</topic><topic>GEF-H1/RhoA/ROCK</topic><topic>Guanine Nucleotide Exchange Factors</topic><topic>Hypertrophy</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>microtubule</topic><topic>Microtubules - drug effects</topic><topic>Microtubules - metabolism</topic><topic>multi-layered hypertrophied MEE</topic><topic>Nocodazole - pharmacology</topic><topic>Organ Culture Techniques</topic><topic>palatal fusion</topic><topic>Palate - drug effects</topic><topic>Palate - embryology</topic><topic>Palate - metabolism</topic><topic>Pregnancy</topic><topic>Proto-Oncogene Proteins</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Rho Guanine Nucleotide Exchange Factors</topic><topic>rhoA GTP-Binding Protein - genetics</topic><topic>rhoA GTP-Binding Protein - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Transforming Growth Factor beta - genetics</topic><topic>Transforming Growth Factor beta - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kitase, Yukiko</creatorcontrib><creatorcontrib>Shuler, Charles F.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Developmental dynamics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kitase, Yukiko</au><au>Shuler, Charles F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multi-Layered hypertrophied MEE formation by microtubule disruption via GEF-H1/RhoA/ROCK signaling pathway</atitle><jtitle>Developmental dynamics</jtitle><addtitle>Dev. Dyn</addtitle><date>2012-07</date><risdate>2012</risdate><volume>241</volume><issue>7</issue><spage>1169</spage><epage>1182</epage><pages>1169-1182</pages><issn>1058-8388</issn><eissn>1097-0177</eissn><abstract>Background: Formation of the secondary palate is complex and disturbance during palatal fusion may result in cleft palate. The processes of adhesion, intercalation, and disappearance of medial edge epithelia (MEE) are characterized by morphological changes requiring dynamic cytoskeletal rearrangement. Microtubules are one of the cytoskeletal elements involved in maintenance of cell morphology. Microtubule‐disrupting drugs have been reported to cause craniofacial malformations including cleft palate. The mechanisms underlying the failure of palatal fusion remain poorly understood. We evaluated the effect of nocodazole (NDZ), a drug that disrupts microtubules, on palatal fusion in organ culture. Results: NDZ caused failure of palatal fusion due to the induction of a multi‐layered hypertrophied MEE in the mid‐region of the secondary palatal shelves. Microtubule disruption increased RhoA activity and stress fiber formation. Pharmacological inhibition of the RhoA/ROCK pathway blocked multi‐layered MEE formation. Partial prevention of hypertrophied MEE was observed with Y27632 and cytochalasin, but not with blebbistatin. NDZ induced re‐localization of GEF‐H1 into cytoplasm from cell–cell junctions. Conclusions: The present study provided evidence that the GEF‐H1/RhoA/ROCK pathway plays a pivotal role in linking microtubule disassembly to the remodeling of the actin cytoskeleton, which resulted in a multi‐layered hypertrophied MEE and failure of palatal fusion. Developmental Dynamics 241:1169–1182, 2012. © 2012 Wiley Periodicals, Inc.
Key findings:
Microtubule disassembly causes failure of palatal fusion due to multi‐layered hypertrophied MEE formation in the middle region of the palatal shelves.
Nocodazole activates RhoA/ROCK signaling pathway and stress fiber formation in MEE
Multi‐layered hypertrophied MEE formation is not dependent on TGF‐β/Smad signaling.
GEF‐H1/RhoA/ROCK signaling pathway is involved in multi‐layred hypertrophied MEE formation.</abstract><cop>New York</cop><pub>Wiley-Liss, Inc</pub><pmid>22565548</pmid><doi>10.1002/dvdy.23800</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Access via Wiley Online Library; EZB-FREE-00999 freely available EZB journals; Wiley Online Library (Open Access Collection); Alma/SFX Local Collection |
| subjects | Animals Blotting, Western Cell Proliferation - drug effects Female Fluorescent Antibody Technique GEF-H1/RhoA/ROCK Guanine Nucleotide Exchange Factors Hypertrophy Mice Mice, Inbred C57BL Mice, Knockout microtubule Microtubules - drug effects Microtubules - metabolism multi-layered hypertrophied MEE Nocodazole - pharmacology Organ Culture Techniques palatal fusion Palate - drug effects Palate - embryology Palate - metabolism Pregnancy Proto-Oncogene Proteins Real-Time Polymerase Chain Reaction Rho Guanine Nucleotide Exchange Factors rhoA GTP-Binding Protein - genetics rhoA GTP-Binding Protein - metabolism Signal Transduction - drug effects Transforming Growth Factor beta - genetics Transforming Growth Factor beta - metabolism |
| title | Multi-Layered hypertrophied MEE formation by microtubule disruption via GEF-H1/RhoA/ROCK signaling pathway |
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