File:Hindlimb Tbx2 model.jpg - Revision history

Z8600021: /* Model of Tbx2 function in the posterior hindlimb mesenchyme */

2019-04-04T23:43:39Z

Model of Tbx2 function in the posterior hindlimb mesenchyme

← Older revision		Revision as of 10:43, 5 April 2019
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	:'''Links:''' [[Musculoskeletal System - Limb Development\|Limb Development]] \| {{TBX}}\| {{Mouse}}		:'''Links:''' [[Musculoskeletal System - Limb Development\|Limb Development]] \| {{TBX}} \| {{Mouse}}
	<br>		<br>
	{{Tbx family collapsetable}}		{{Tbx family collapsetable}}

Z8600021: /* Model of Tbx2 function in the posterior hindlimb mesenchyme */

2019-04-04T23:43:24Z

Model of Tbx2 function in the posterior hindlimb mesenchyme

← Older revision		Revision as of 10:43, 5 April 2019
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	:'''Links:''' [[Musculoskeletal System - Limb Development\|Limb Development]] \| {{~~Tbx~~}}\| {{Mouse}}		:'''Links:''' [[Musculoskeletal System - Limb Development\|Limb Development]] \| {{TBX}}\| {{Mouse}}
	<br>		<br>
	{{Tbx family collapsetable}}		{{Tbx family collapsetable}}

Z8600021 at 23:42, 4 April 2019

2019-04-04T23:42:55Z

← Older revision		Revision as of 10:42, 5 April 2019
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	==Model of Tbx2 function in the posterior hindlimb mesenchyme==		==Model of Tbx2 function in the posterior hindlimb mesenchyme==

	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. Failure of Grem1 repression in Tbx2-deficient hindlimbs causes prolonged e-m signaling.		During normal limb bud outgrowth ({{ME10.5}}) 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 ({{ME11.5}}, dotted arrows). The diagrams illustrate these dynamic signaling activities. Failure of Grem1 repression in Tbx2-deficient hindlimbs causes prolonged e-m signaling.


	:'''Links:''' [[Musculoskeletal System - Limb Development\|Limb Development]] \| ~~[[Developmental_Signals -~~ Tbx\|~~Tbx]] \| [[~~Mouse ~~Development]]~~		:'''Links:''' [[Musculoskeletal System - Limb Development\|Limb Development]] \| {{Tbx}}\| {{Mouse}}
			<br>
	{{Tbx family collapsetable}}		{{Tbx family collapsetable}}
	===Reference===		===Reference===

	~~<pubmed>~~23633963~~</pubmed>\| [http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003467 PLoS Genet.]~~		{{#pmid:23633963}}


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

			{{Footer}}
	[[Category:Mouse]][[Category:Limb]][[Category:Tbx]][[Category:Cartoon]]		[[Category:Mouse]][[Category:Limb]][[Category:Tbx]][[Category:Cartoon]]
	[[Category:Mouse E10.5]][[Category:Mouse E11.5]][[Category:Mouse E12.5]]		[[Category:Mouse E10.5]][[Category:Mouse E11.5]][[Category:Mouse E12.5]]

Z8600021 at 04:43, 16 Ocak 2018

2018-01-16T04:43:13Z

← Older revision		Revision as of 15:43, 16 Ocak 2018
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	:'''Links:''' [[Musculoskeletal System - Limb Development\|Limb Development]] \| [[Developmental_Signals - Tbx\|Tbx]] \| [[Mouse Development]]		:'''Links:''' [[Musculoskeletal System - Limb Development\|Limb Development]] \| [[Developmental_Signals - Tbx\|Tbx]] \| [[Mouse Development]]

			{{Tbx family collapsetable}}
	===Reference===		===Reference===

Z8600021 at 01:16, 7 December 2014

2014-12-07T01:16:12Z

← Older revision		Revision as of 12:16, 7 December 2014
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	:'''Links:''' [[Musculoskeletal System - Limb Development\|Limb Development]] \| [[~~Developmental_Signals_Tbx~~\|Tbx]] \| [[Mouse Development]]		:'''Links:''' [[Musculoskeletal System - Limb Development\|Limb Development]] \| [[Developmental_Signals - Tbx\|Tbx]] \| [[Mouse Development]]
	===Reference===		===Reference===

Z8600021: /* Model of Tbx2 function in the posterior hindlimb mesenchyme */

2014-12-07T00:53:01Z

Model of Tbx2 function in the posterior hindlimb mesenchyme

← Older revision		Revision as of 11:53, 7 December 2014
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			:'''Links:''' [[Musculoskeletal System - Limb Development\|Limb Development]] \| [[Developmental_Signals_Tbx\|Tbx]] \| [[Mouse Development]]
	===Reference===		===Reference===

Z8600021 at 00:51, 7 December 2014

2014-12-07T00:51:00Z

← Older revision		Revision as of 11:51, 7 December 2014
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	==Model of Tbx2 function in the posterior hindlimb mesenchyme==		==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).		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. Failure of Grem1 repression in Tbx2-deficient hindlimbs causes prolonged e-m signaling.


	===Reference===		===Reference===

	<pubmed>23633963<pubmed>\| [http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003467 PLoS Genet.]		<pubmed>23633963</pubmed>\| [http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003467 PLoS Genet.]

Z8600021 at 00:50, 7 December 2014

2014-12-07T00:50:05Z

← Older revision		Revision as of 11:50, 7 December 2014
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	~~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~~

Z8600021: ==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...

2014-12-07T00:48:17Z

New page

==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>| [http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003467 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.

PLoS Genet. 2013;9(4):e1003467. doi: 10.1371/journal.pgen.1003467. Epub 2013 Apr 25.
Tbx2 terminates shh/fgf signaling in the developing mouse limb bud by direct repression of gremlin1.
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