%0 Journal Article
%T Tgf¦Â2 and 3 are coexpressed with their extracellular regulator Ltbp1 in the early limb bud and modulate mesodermal outgrowth and BMP signaling in chicken embryos
%A Carlos I Lorda-Diez
%A Juan A Montero
%A Juan A Garcia-Porrero
%A Juan M Hurle
%J BMC Developmental Biology
%D 2010
%I BioMed Central
%R 10.1186/1471-213x-10-69
%X Immunohistochemical detection of phosphorylated Smad2 and Smad3 indicates that signaling by this pathway is active in the undifferentiated mesoderm and AER. Gene expression analysis shows that transcripts of tgf¦Â2 and tgf¦Â3 but not tgf¦Â1 are abundant in the growing undifferentiated limb mesoderm. Transcripts of tgf¦Â2 are also found in the AER, which is the signaling center responsible for limb outgrowth. Furthermore, we show that Latent Tgf¦Â Binding protein 1 (LTBP1), which is a key extracellular modulator of Tgf¦Â ligand bioavailability, is coexpressed with Tgf¦Âs in the early limb bud. Administration of exogenous Tgf¦Âs to limb buds growing in explant cultures provides evidence of these cytokines playing a role in the regulation of mesodermal limb proliferation. In addition, analysis of gene regulation in these experiments revealed that Tgf¦Â signaling has no effect on the expression of master genes of musculoskeletal tissue differentiation but negatively regulates the expression of the BMP-antagonist Gremlin.We propose the occurrence of an interplay between Tgf¦Â and BMP signaling functionally associated with the regulation of early limb outgrowth by modulating limb mesenchymal cell proliferation.Tgf¦Âs constitute a subfamily formed in birds and mammals by 3 isoforms of secreted cytokines (Tgf¦Â1; Tgf¦Â2; Tgf¦Â3), which gives the name to the large Tgf¦Â superfamily made up of more than 30 structurally related proteins that comprises Activins, BMPs and GDFs. Tgf¦Âs are multifunctional factors with important regulatory roles in adult and embryonic systems. During development Tgf¦Âs are able to regulate almost all basic cellular processes including migration, proliferation, apoptosis and differentiation (reviewed by [1]). Their effects are mediated by binding to specific cell surface transmembrane receptors with serine/threonine kinase activity that trigger an intracellular cascade which regulates the expression of target genes and the biogenesis of specific microRNAs (reviewed
%U http://www.biomedcentral.com/1471-213X/10/69