scholarly journals Differential regulation of gene expression in the digit forming area of the mouse limb bud by SHH and gremlin 1/FGF-mediated epithelial-mesenchymal signalling

Development ◽  
2006 ◽  
Vol 133 (17) ◽  
pp. 3419-3428 ◽  
Author(s):  
L. Panman
Development ◽  
2021 ◽  
Author(s):  
Julie Gamart ◽  
Iros Barozzi ◽  
Frédéric Laurent ◽  
Robert Reinhardt ◽  
Laurène Ramos Martins ◽  
...  

SMAD4 regulates gene expression in response to BMP and TGFβ signal transduction and is required for diverse morphogenetic processes, but its target genes have remained largely elusive. Here, we identify the SMAD4 target genes in mouse limb buds using an epitope-tagged Smad4 allele for ChIP-seq analysis in combination with transcription profiling. This analysis shows that SMAD4 predominantly mediates BMP signal-transduction during early limb bud development. Unexpectedly, the expression of cholesterol biosynthesis enzymes is precociously down-regulated and intracellular cholesterol levels are reduced in Smad4-deficient limb bud mesenchymal progenitors. Most importantly, our analysis reveals a predominant function of SMAD4 in up-regulating target genes in the anterior limb bud mesenchyme. Analysis of differentially expressed genes shared between Smad4- and Shh-deficient limb buds corroborates this function of SMAD4 and also reveals the repressive effect of SMAD4 on posterior genes that are up-regulated in response to SHH signaling. This analysis uncovers opposing trans-regulatory inputs from SHH and SMAD4-mediated BMP signal transduction on anterior and posterior gene expression during the digit patterning and outgrowth in early limb buds.


Development ◽  
1992 ◽  
Vol 115 (2) ◽  
pp. 553-560 ◽  
Author(s):  
J.C. Izpisua-Belmonte ◽  
J.M. Brown ◽  
A. Crawley ◽  
D. Duboule ◽  
C. Tickle

The products of Hox-4 genes appear to encode position in developing vertebrate limbs. In chick embryos, a number of different signalling regions when grafted to wing buds lead to duplicated digit patterns. We grafted tissue from the equivalent regions in mouse embryos to chick wing buds and assayed expression of Hox-4 genes in both the mouse cells in the grafts and in the chick cells in the responding limb bud using species specific probes. Tissue from the mouse limb polarizing region and anterior primitive streak respecify anterior chick limb bud cells to give posterior structures and lead to activation of all the genes in the complex. Mouse neural tube and genital tubercle grafts, which give much less extensive changes in pattern, do not activate 5′-located Hox-4 genes. Analysis of expression of Hox-4 genes in mouse cells in the grafted signalling regions reveals no relationship between expression of these genes and strength of their signalling activity. Endogenous signals in the chick limb bud activate Hox-4 genes in grafts of mouse anterior limb cells when placed posteriorly and in grafts of mouse anterior primitive streak tissue. The activation of the same gene network by different signalling regions points to a similarity in patterning mechanisms along the axes of the vertebrate body.


2004 ◽  
Vol 325 (3) ◽  
pp. 892-898 ◽  
Author(s):  
Jeong-Hwa Heo ◽  
Su-Jin Jeong ◽  
Ja-Whan Seol ◽  
Hye-Jin Kim ◽  
Jeong-Whan Han ◽  
...  

2002 ◽  
Vol 277 (28) ◽  
pp. 25001-25010 ◽  
Author(s):  
Carol J. Cox ◽  
Herbert M. Espinoza ◽  
Bryan McWilliams ◽  
Kimberly Chappell ◽  
Lisa Morton ◽  
...  

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