Opposing RA and FGF signals control proximodistal vertebrate limb development through regulation of Meis genes
Vertebrate limbs develop in a temporal proximodistal sequence, with proximal regions specified and generated earlier than distal ones. Whereas considerable information is available on the mechanisms promoting limb growth, those involved in determining the proximodistal identity of limb parts remain...
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| Veröffentlicht in: | Development (Cambridge) 2000-09, Vol.127 (18), p.3961-3970 |
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| creator | Mercader, Nadia Leonardo, Esther Piedra, María Elisa Martínez-A, Carlos Ángeles Ros, María Torres, Miguel |
| description | Vertebrate limbs develop in a temporal proximodistal sequence, with proximal regions specified and generated earlier than distal ones. Whereas considerable information is available on the mechanisms promoting limb growth, those involved in determining the proximodistal identity of limb parts remain largely unknown. We show here that retinoic acid (RA) is an upstream activator of the proximal determinant genes Meis1 and Meis2. RA promotes proximalization of limb cells and endogenous RA signaling is required to maintain the proximal Meis domain in the limb. RA synthesis and signaling range, which initially span the entire lateral plate mesoderm, become restricted to proximal limb domains by the apical ectodermal ridge (AER) activity following limb initiation. We identify fibroblast growth factor (FGF) as the main molecule responsible for this AER activity and propose a model integrating the role of FGF in limb cell proliferation, with a specific function in promoting distalization through inhibition of RA production and signaling. |
| doi_str_mv | 10.1242/dev.127.18.3961 |
| format | Article |
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Whereas considerable information is available on the mechanisms promoting limb growth, those involved in determining the proximodistal identity of limb parts remain largely unknown. We show here that retinoic acid (RA) is an upstream activator of the proximal determinant genes Meis1 and Meis2. RA promotes proximalization of limb cells and endogenous RA signaling is required to maintain the proximal Meis domain in the limb. RA synthesis and signaling range, which initially span the entire lateral plate mesoderm, become restricted to proximal limb domains by the apical ectodermal ridge (AER) activity following limb initiation. 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Whereas considerable information is available on the mechanisms promoting limb growth, those involved in determining the proximodistal identity of limb parts remain largely unknown. We show here that retinoic acid (RA) is an upstream activator of the proximal determinant genes Meis1 and Meis2. RA promotes proximalization of limb cells and endogenous RA signaling is required to maintain the proximal Meis domain in the limb. RA synthesis and signaling range, which initially span the entire lateral plate mesoderm, become restricted to proximal limb domains by the apical ectodermal ridge (AER) activity following limb initiation. We identify fibroblast growth factor (FGF) as the main molecule responsible for this AER activity and propose a model integrating the role of FGF in limb cell proliferation, with a specific function in promoting distalization through inhibition of RA production and signaling.</description><subject>Animals</subject><subject>Body Patterning - genetics</subject><subject>Chick Embryo</subject><subject>Ectoderm - metabolism</subject><subject>Extremities - embryology</subject><subject>Fibroblast Growth Factors - pharmacology</subject><subject>Gene Expression Regulation, Developmental - drug effects</subject><subject>Genes, Homeobox - genetics</subject><subject>Homeodomain Proteins - genetics</subject><subject>In Situ Hybridization</subject><subject>Limb Buds - drug effects</subject><subject>Limb Buds - metabolism</subject><subject>Limb Buds - transplantation</subject><subject>Meis1 gene</subject><subject>meis2 gene</subject><subject>Microscopy, Fluorescence</subject><subject>Models, Biological</subject><subject>Myeloid Ecotropic Viral Integration Site 1 Protein</subject><subject>Neoplasm Proteins - genetics</subject><subject>retinoic acid</subject><subject>RNA, Messenger - analysis</subject><subject>RNA, Messenger - genetics</subject><subject>Signal Transduction - drug effects</subject><subject>Tretinoin - antagonists & inhibitors</subject><subject>Tretinoin - metabolism</subject><subject>Tretinoin - pharmacology</subject><subject>Vertebrata</subject><issn>0950-1991</issn><issn>1477-9129</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1v3CAQQFHUKtl8nHurOPXmDYM_MMco6qaVUkWq2jMCe9ZLhcEFnKT_vkS7h_bESDyehkfIB2Bb4A2_HfG5DGIL_baWHZyRDTRCVBK4fEc2TLasAinhglym9IsxVndCnJMLKDe8l82G-KdlCcn6iX6_o9qPdPewo8lOXrtEh-BzDI4uMbzaOYw2Ze3oM8aMJuqM1NnZ0LIDurDM6DPNhxjW6UAjTqvT2QZPw55-Q5vohB7TNXm_L2a8OZ1X5Ofu84_7L9Xj08PX-7vHamgEy5UxAjTsOa85ytE0cjCCM4l1IzvkbdvxusEWoIXatM3Q1mMHHLTpetkbzVl9RT4dvWX13yumrGabBnROewxrUiCKggso4O0RHGJIKeJeLdHOOv5RwNRbYlW-VwahoFdvicuLjyf1amYc_-GPTQuwPQIHOx1ebERlbHBhKvWSOsX6z_gXzFeIkg</recordid><startdate>20000915</startdate><enddate>20000915</enddate><creator>Mercader, Nadia</creator><creator>Leonardo, Esther</creator><creator>Piedra, María Elisa</creator><creator>Martínez-A, Carlos</creator><creator>Ángeles Ros, María</creator><creator>Torres, Miguel</creator><general>The Company of Biologists Limited</general><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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20000915</creationdate><title>Opposing RA and FGF signals control proximodistal vertebrate limb development through regulation of Meis genes</title><author>Mercader, Nadia ; Leonardo, Esther ; Piedra, María Elisa ; Martínez-A, Carlos ; Ángeles Ros, María ; Torres, Miguel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-bb71a1f2232e9db49cb7209e3496e2556234e511513b54c53d6121ab6898ba203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Body Patterning - genetics</topic><topic>Chick Embryo</topic><topic>Ectoderm - metabolism</topic><topic>Extremities - embryology</topic><topic>Fibroblast Growth Factors - pharmacology</topic><topic>Gene Expression Regulation, Developmental - drug effects</topic><topic>Genes, Homeobox - genetics</topic><topic>Homeodomain Proteins - genetics</topic><topic>In Situ Hybridization</topic><topic>Limb Buds - drug effects</topic><topic>Limb Buds - metabolism</topic><topic>Limb Buds - transplantation</topic><topic>Meis1 gene</topic><topic>meis2 gene</topic><topic>Microscopy, Fluorescence</topic><topic>Models, Biological</topic><topic>Myeloid Ecotropic Viral Integration Site 1 Protein</topic><topic>Neoplasm Proteins - genetics</topic><topic>retinoic acid</topic><topic>RNA, Messenger - analysis</topic><topic>RNA, Messenger - genetics</topic><topic>Signal Transduction - drug effects</topic><topic>Tretinoin - antagonists & inhibitors</topic><topic>Tretinoin - metabolism</topic><topic>Tretinoin - pharmacology</topic><topic>Vertebrata</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mercader, Nadia</creatorcontrib><creatorcontrib>Leonardo, Esther</creatorcontrib><creatorcontrib>Piedra, María Elisa</creatorcontrib><creatorcontrib>Martínez-A, Carlos</creatorcontrib><creatorcontrib>Ángeles Ros, María</creatorcontrib><creatorcontrib>Torres, Miguel</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Development (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mercader, Nadia</au><au>Leonardo, Esther</au><au>Piedra, María Elisa</au><au>Martínez-A, Carlos</au><au>Ángeles Ros, María</au><au>Torres, Miguel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Opposing RA and FGF signals control proximodistal vertebrate limb development through regulation of Meis genes</atitle><jtitle>Development (Cambridge)</jtitle><addtitle>Development</addtitle><date>2000-09-15</date><risdate>2000</risdate><volume>127</volume><issue>18</issue><spage>3961</spage><epage>3970</epage><pages>3961-3970</pages><issn>0950-1991</issn><eissn>1477-9129</eissn><abstract>Vertebrate limbs develop in a temporal proximodistal sequence, with proximal regions specified and generated earlier than distal ones. Whereas considerable information is available on the mechanisms promoting limb growth, those involved in determining the proximodistal identity of limb parts remain largely unknown. We show here that retinoic acid (RA) is an upstream activator of the proximal determinant genes Meis1 and Meis2. RA promotes proximalization of limb cells and endogenous RA signaling is required to maintain the proximal Meis domain in the limb. RA synthesis and signaling range, which initially span the entire lateral plate mesoderm, become restricted to proximal limb domains by the apical ectodermal ridge (AER) activity following limb initiation. We identify fibroblast growth factor (FGF) as the main molecule responsible for this AER activity and propose a model integrating the role of FGF in limb cell proliferation, with a specific function in promoting distalization through inhibition of RA production and signaling.</abstract><cop>England</cop><pub>The Company of Biologists Limited</pub><pmid>10952894</pmid><doi>10.1242/dev.127.18.3961</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Company of Biologists |
| subjects | Animals Body Patterning - genetics Chick Embryo Ectoderm - metabolism Extremities - embryology Fibroblast Growth Factors - pharmacology Gene Expression Regulation, Developmental - drug effects Genes, Homeobox - genetics Homeodomain Proteins - genetics In Situ Hybridization Limb Buds - drug effects Limb Buds - metabolism Limb Buds - transplantation Meis1 gene meis2 gene Microscopy, Fluorescence Models, Biological Myeloid Ecotropic Viral Integration Site 1 Protein Neoplasm Proteins - genetics retinoic acid RNA, Messenger - analysis RNA, Messenger - genetics Signal Transduction - drug effects Tretinoin - antagonists & inhibitors Tretinoin - metabolism Tretinoin - pharmacology Vertebrata |
| title | Opposing RA and FGF signals control proximodistal vertebrate limb development through regulation of Meis genes |
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