Joint interpretation of AER/FGF and ZPA/SHH over time and space underlies hairy2 expression in the chick limb
Summary Embryo development requires precise orchestration of cell proliferation and differentiation in both time and space. A molecular clock operating through gene expression oscillations was first described in the presomitic mesoderm (PSM) underlying periodic somite formation. Cycles of HES gene e...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2012-08-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/1/11/1102 |
| _version_ | 1818859805762125824 |
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| author | Caroline J. Sheeba Raquel P. Andrade Isabel Palmeirim |
| author_facet | Caroline J. Sheeba Raquel P. Andrade Isabel Palmeirim |
| author_sort | Caroline J. Sheeba |
| collection | DOAJ |
| description | Summary
Embryo development requires precise orchestration of cell proliferation and differentiation in both time and space. A molecular clock operating through gene expression oscillations was first described in the presomitic mesoderm (PSM) underlying periodic somite formation. Cycles of HES gene expression have been further identified in other progenitor cells, including the chick distal limb mesenchyme, embryonic neural progenitors and both mesenchymal and embryonic stem cells. In the limb, hairy2 is expressed in the distal mesenchyme, adjacent to the FGF source (AER) and along the ZPA-derived SHH gradient, the two major regulators of limb development. Here we report that hairy2 expression depends on joint AER/FGF and ZPA/SHH signaling. FGF plays an instructive role on hairy2, mediated by Erk and Akt pathway activation, while SHH acts by creating a permissive state defined by Gli3-A/Gli3-R>1. Moreover, we show that AER/FGF and ZPA/SHH present distinct temporal and spatial signaling properties in the distal limb mesenchyme: SHH acts at a long-term, long-range on hairy2, while FGF has a short-term, short-range action. Our work establishes limb hairy2 expression as an output of integrated FGF and SHH signaling in time and space, providing novel clues for understanding the regulatory mechanisms underlying HES oscillations in multiple systems, including embryonic stem cell pluripotency. |
| first_indexed | 2024-12-19T09:18:01Z |
| format | Article |
| id | doaj.art-b09d217753244b6cb27c5c77e5162080 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-19T09:18:01Z |
| publishDate | 2012-08-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-b09d217753244b6cb27c5c77e51620802022-12-21T20:28:04ZengThe Company of BiologistsBiology Open2046-63902012-08-011111102111010.1242/bio.2012238620122386Joint interpretation of AER/FGF and ZPA/SHH over time and space underlies hairy2 expression in the chick limbCaroline J. Sheeba0Raquel P. Andrade1Isabel Palmeirim2 Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal Regenerative Medicine Program, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 8005-139 Faro, Portugal; IBB-Institute for Biotechnology and Bioengineering, Centro de Biomedicina Molecular e Estrutural, Universidade do Algarve, 8005-139 Faro, Portugal Summary Embryo development requires precise orchestration of cell proliferation and differentiation in both time and space. A molecular clock operating through gene expression oscillations was first described in the presomitic mesoderm (PSM) underlying periodic somite formation. Cycles of HES gene expression have been further identified in other progenitor cells, including the chick distal limb mesenchyme, embryonic neural progenitors and both mesenchymal and embryonic stem cells. In the limb, hairy2 is expressed in the distal mesenchyme, adjacent to the FGF source (AER) and along the ZPA-derived SHH gradient, the two major regulators of limb development. Here we report that hairy2 expression depends on joint AER/FGF and ZPA/SHH signaling. FGF plays an instructive role on hairy2, mediated by Erk and Akt pathway activation, while SHH acts by creating a permissive state defined by Gli3-A/Gli3-R>1. Moreover, we show that AER/FGF and ZPA/SHH present distinct temporal and spatial signaling properties in the distal limb mesenchyme: SHH acts at a long-term, long-range on hairy2, while FGF has a short-term, short-range action. Our work establishes limb hairy2 expression as an output of integrated FGF and SHH signaling in time and space, providing novel clues for understanding the regulatory mechanisms underlying HES oscillations in multiple systems, including embryonic stem cell pluripotency.http://bio.biologists.org/content/1/11/1102Fibroblast growth factorHES expressionLimb developmentSonic hedgehog |
| spellingShingle | Caroline J. Sheeba Raquel P. Andrade Isabel Palmeirim Joint interpretation of AER/FGF and ZPA/SHH over time and space underlies hairy2 expression in the chick limb Biology Open Fibroblast growth factor HES expression Limb development Sonic hedgehog |
| title | Joint interpretation of AER/FGF and ZPA/SHH over time and space underlies hairy2 expression in the chick limb |
| title_full | Joint interpretation of AER/FGF and ZPA/SHH over time and space underlies hairy2 expression in the chick limb |
| title_fullStr | Joint interpretation of AER/FGF and ZPA/SHH over time and space underlies hairy2 expression in the chick limb |
| title_full_unstemmed | Joint interpretation of AER/FGF and ZPA/SHH over time and space underlies hairy2 expression in the chick limb |
| title_short | Joint interpretation of AER/FGF and ZPA/SHH over time and space underlies hairy2 expression in the chick limb |
| title_sort | joint interpretation of aer fgf and zpa shh over time and space underlies hairy2 expression in the chick limb |
| topic | Fibroblast growth factor HES expression Limb development Sonic hedgehog |
| url | http://bio.biologists.org/content/1/11/1102 |
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