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A regulatory network of two galectins mediates the earliest steps of avian limb skeletal morphogenesis

BACKGROUND: The skeletal elements of vertebrate embryonic limbs are prefigured by rod- and spot-like condensations of precartilage mesenchymal cells. The formation of these condensations depends on cell-matrix and cell-cell interactions, but how they are initiated and patterned is as yet unresolved....

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Autores principales: Bhat, Ramray, Lerea, Kenneth M, Peng, Hong, Kaltner, Herbert, Gabius, Hans-Joachim, Newman, Stuart A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042966/
https://www.ncbi.nlm.nih.gov/pubmed/21284876
http://dx.doi.org/10.1186/1471-213X-11-6
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author Bhat, Ramray
Lerea, Kenneth M
Peng, Hong
Kaltner, Herbert
Gabius, Hans-Joachim
Newman, Stuart A
author_facet Bhat, Ramray
Lerea, Kenneth M
Peng, Hong
Kaltner, Herbert
Gabius, Hans-Joachim
Newman, Stuart A
author_sort Bhat, Ramray
collection PubMed
description BACKGROUND: The skeletal elements of vertebrate embryonic limbs are prefigured by rod- and spot-like condensations of precartilage mesenchymal cells. The formation of these condensations depends on cell-matrix and cell-cell interactions, but how they are initiated and patterned is as yet unresolved. RESULTS: Here we provide evidence that galectins, β-galactoside-binding lectins with β-sandwich folding, play fundamental roles in these processes. We show that among the five chicken galectin (CG) genes, two, CG-1A, and CG-8, are markedly elevated in expression at prospective sites of condensation in vitro and in vivo, with their protein products appearing earlier in development than any previously described marker. The two molecules enhance one another's gene expression but have opposite effects on condensation formation and cartilage development in vivo and in vitro: CG-1A, a non-covalent homodimer, promotes this process, while the tandem-repeat-type CG-8 antagonizes it. Correspondingly, knockdown of CG-1A inhibits the formation of skeletal elements while knockdown of CG-8 enhances it. The apparent paradox of mutual activation at the gene expression level coupled with antagonistic roles in skeletogenesis is resolved by analysis of the direct effect of the proteins on precartilage cells. Specifically, CG-1A causes their aggregation, whereas CG-8, which has no adhesive function of its own, blocks this effect. The developmental appearance and regulation of the unknown cell surface moieties ("ligands") to which CG-1A and CG-8 bind were indicative of specific cognate- and cross-regulatory interactions. CONCLUSION: Our findings indicate that CG-1A and CG-8 constitute a multiscale network that is a major mediator, earlier-acting than any previously described, of the formation and patterning of precartilage mesenchymal condensations in the developing limb. This network functions autonomously of limb bud signaling centers or other limb bud positional cues.
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spelling pubmed-30429662011-02-23 A regulatory network of two galectins mediates the earliest steps of avian limb skeletal morphogenesis Bhat, Ramray Lerea, Kenneth M Peng, Hong Kaltner, Herbert Gabius, Hans-Joachim Newman, Stuart A BMC Dev Biol Research Article BACKGROUND: The skeletal elements of vertebrate embryonic limbs are prefigured by rod- and spot-like condensations of precartilage mesenchymal cells. The formation of these condensations depends on cell-matrix and cell-cell interactions, but how they are initiated and patterned is as yet unresolved. RESULTS: Here we provide evidence that galectins, β-galactoside-binding lectins with β-sandwich folding, play fundamental roles in these processes. We show that among the five chicken galectin (CG) genes, two, CG-1A, and CG-8, are markedly elevated in expression at prospective sites of condensation in vitro and in vivo, with their protein products appearing earlier in development than any previously described marker. The two molecules enhance one another's gene expression but have opposite effects on condensation formation and cartilage development in vivo and in vitro: CG-1A, a non-covalent homodimer, promotes this process, while the tandem-repeat-type CG-8 antagonizes it. Correspondingly, knockdown of CG-1A inhibits the formation of skeletal elements while knockdown of CG-8 enhances it. The apparent paradox of mutual activation at the gene expression level coupled with antagonistic roles in skeletogenesis is resolved by analysis of the direct effect of the proteins on precartilage cells. Specifically, CG-1A causes their aggregation, whereas CG-8, which has no adhesive function of its own, blocks this effect. The developmental appearance and regulation of the unknown cell surface moieties ("ligands") to which CG-1A and CG-8 bind were indicative of specific cognate- and cross-regulatory interactions. CONCLUSION: Our findings indicate that CG-1A and CG-8 constitute a multiscale network that is a major mediator, earlier-acting than any previously described, of the formation and patterning of precartilage mesenchymal condensations in the developing limb. This network functions autonomously of limb bud signaling centers or other limb bud positional cues. BioMed Central 2011-02-01 /pmc/articles/PMC3042966/ /pubmed/21284876 http://dx.doi.org/10.1186/1471-213X-11-6 Text en Copyright ©2011 Bhat et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Bhat, Ramray
Lerea, Kenneth M
Peng, Hong
Kaltner, Herbert
Gabius, Hans-Joachim
Newman, Stuart A
A regulatory network of two galectins mediates the earliest steps of avian limb skeletal morphogenesis
title A regulatory network of two galectins mediates the earliest steps of avian limb skeletal morphogenesis
title_full A regulatory network of two galectins mediates the earliest steps of avian limb skeletal morphogenesis
title_fullStr A regulatory network of two galectins mediates the earliest steps of avian limb skeletal morphogenesis
title_full_unstemmed A regulatory network of two galectins mediates the earliest steps of avian limb skeletal morphogenesis
title_short A regulatory network of two galectins mediates the earliest steps of avian limb skeletal morphogenesis
title_sort regulatory network of two galectins mediates the earliest steps of avian limb skeletal morphogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042966/
https://www.ncbi.nlm.nih.gov/pubmed/21284876
http://dx.doi.org/10.1186/1471-213X-11-6
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