File:Hindlimb Tbx2 model.jpg: Difference between revisions

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Model of Tbx2 function in the posterior hindlimb mesenchyme

(A) During normal limb bud outgrowth (E10.5) the expression domains of Shh (red), Grem1 (yellow) and Fgf4/9/17 (green) are in close proximity allowing propagation of the e-m signaling loop. Following proliferative expansion of ZPA-derived cells, a broadened Tbx2 expression (blue) causes Grem1 repression. Progressive displacement of Grem1-secreting cells from the AER terminates e-m signaling (E11.5, dotted arrows). The diagrams illustrate these dynamic signaling activities. (B) Failure of Grem1 repression in Tbx2-deficient hindlimbs causes prolonged e-m signaling. The dotted line shows the posterior limit of Grem1 expression in the wild-type. Impaired termination of outgrowth reduces apoptosis and causes expansion of the digit4 condensation (E12.5, grey regions).

Reference

<pubmed>23633963<pubmed>| PLoS Genet.

Copyright

© 2013 Farin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Figure 7. doi:10.1371/journal.pgen.1003467.g007 Original figure cropped, adjusted in size and labelling.

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	Date/Time	Thumbnail	Dimensions	User	Comment
current	10:48, 7 December 2014		1,000 × 607 (84 KB)	Z8600021 (talk \| contribs)	==Model of Tbx2 function in the posterior hindlimb mesenchyme== (A) During normal limb bud outgrowth (E10.5) the expression domains of Shh (red), Grem1 (yellow) and Fgf4/9/17 (green) are in close proximity allowing propagation of the e-m signaling loo...

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Copyright holder	Creative Commons Attribution License
Copyright status	Copyright status not set
Software used	Adobe Photoshop CS2 Windows
Short title	Figure 7
IIM version	2

@@ Line 15: / Line 15: @@
-PLoS Genet. 2013;9(4):e1003467. doi: 10.1371/journal.pgen.1003467. Epub 2013 Apr 25.
+[[Category:Mouse]][[Category:Limb]][[Category:Tbx]][[Category:Cartoon]]
-Tbx2 terminates shh/fgf signaling in the developing mouse limb bud by direct repression of gremlin1.
+[[Category:Mouse E10.5]][[Category:Mouse E11.5]][[Category:Mouse E12.5]]
-Farin HF1, Lüdtke TH, Schmidt MK, Placzko S, Schuster-Gossler K, Petry M, Christoffels VM, Kispert A.
-Author information
-Abstract
-Vertebrate limb outgrowth is driven by a positive feedback loop that involves Sonic hedgehog (Shh) and Gremlin1 (Grem1) in the posterior limb bud mesenchyme and Fibroblast growth factors (Fgfs) in the overlying epithelium. Proper spatio-temporal control of these signaling activities is required to avoid limb malformations such as polydactyly. Here we show that, in Tbx2-deficient hindlimbs, Shh/Fgf4 signaling is prolonged, resulting in increased limb bud size and duplication of digit 4. In turn, limb-specific Tbx2 overexpression leads to premature termination of this signaling loop with smaller limbs and reduced digit number as phenotypic manifestation. We show that Tbx2 directly represses Grem1 in distal regions of the posterior limb mesenchyme allowing Bone morphogenetic protein (Bmp) signaling to abrogate Fgf4/9/17 expression in the overlying epithelium. Since Tbx2 itself is a target of Bmp signaling, our data identify a growth-inhibiting positive feedback loop (Bmp/Tbx2/Grem1). We propose that proliferative expansion of Tbx2-expressing cells mediates self-termination of limb bud outgrowth due to their refractoriness to Grem1 induction.
-PMID: 23633963