Talk:Musculoskeletal System - Limb Development - Revision history

Z8600021 at 00:05, 18 December 2021

2021-12-18T00:05:49Z

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			==2021==
			{{#pmid:34584102}}


			Conserved and species-specific chromatin remodeling and regulatory dynamics during mouse and chicken limb bud development


			Chromatin remodeling and genomic alterations impact spatio-temporal regulation of gene expression, which is central to embryonic development. The analysis of mouse and chicken limb development provides important insights into the morphoregulatory mechanisms, however little is known about the regulatory differences underlying their morphological divergence. Here, we identify the underlying shared and species-specific epigenomic and genomic variations. In mouse forelimb buds, we observe striking synchrony between the temporal dynamics of chromatin accessibility and gene expression, while their divergence in chicken wing buds uncovers species-specific regulatory heterochrony. In silico mapping of transcription factor binding sites and computational footprinting establishes the developmental time-restricted transcription factor-DNA interactions. Finally, the construction of target gene networks for HAND2 and GLI3 transcriptional regulators reveals both conserved and species-specific interactions. Our analysis reveals the impact of genome evolution on the regulatory interactions orchestrating vertebrate limb bud morphogenesis and provides a molecular framework for comparative Evo-Devo studies.

	==2020==		==2020==

Z8600021 at 01:11, 16 Ocak 2020

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-==2019==
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Z8600021 at 07:23, 22 Ocak 2019

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-==10 Most Recent Papers==
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 Author information
 PMID: 16586709 PMCID: PMC1091226

Z8600021 at 07:22, 22 Ocak 2019

2019-01-22T07:22:26Z

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	scapula - http://www.ncbi.nlm.nih.gov/pubmed/20627960		scapula - http://www.ncbi.nlm.nih.gov/pubmed/20627960

			==Historic==

			===Harrison transplant Experiments===

			Proc Natl Acad Sci U S A. 1924 Feb;10(2):69-74.
			Some Unexpected Results of the Heteroplastic Transplantation of Limbs.
			Harrison RG1.
			Author information
			PMID: 16576784 PMCID: PMC1085516

			Proc Natl Acad Sci U S A. 1917 Apr;3(4):245-51.
			Transplantation of Limbs.
			Harrison RG1.
			Author information
			PMID: 16586709 PMCID: PMC1091226

Z8600021 at 00:18, 1 November 2018

2018-11-01T00:18:26Z

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	==2018==		==2018==

			===A point mutation in the pre-ZRS disrupts sonic hedgehog expression in the limb bud and results in triphalangeal thumb-polysyndactyly syndrome===


			Genet Med. 2018 Mar 15. doi: 10.1038/gim.2018.18. [Epub ahead of print]

			Potuijt JWP1, Baas M1, Sukenik-Halevy R2,3,4, Douben H5, Nguyen P1, Venter DJ6,7,8, Gallagher R6, Swagemakers SM9,10, Hovius SER1, van Nieuwenhoven CA1, Galjaard RH5, van der Spek PJ9,10, Ahituv N2,3, de Klein A5.

			Abstract

			PurposeThe zone of polarizing activity regulatory sequence (ZRS) is an enhancer that regulates sonic hedgehog during embryonic limb development. Recently, mutations in a noncoding evolutionary conserved sequence 500 bp upstream of the ZRS, termed the pre-ZRS (pZRS), have been associated with polydactyly in dogs and humans. Here, we report the first case of triphalangeal thumb-polysyndactyly syndrome (TPT-PS) to be associated with mutations in this region and show via mouse enhancer assays how this mutation leads to ectopic expression throughout the developing limb bud.MethodsWe used linkage analysis, whole-exome sequencing, Sanger sequencing, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, single-nucleotide polymorphism array, and a mouse transgenic enhancer assay.ResultsTen members of a TPT-PS family were included in this study. The mutation was linked to chromosome 7q36 (LOD score 3.0). No aberrations in the ZRS could be identified. A point mutation in the pZRS (chr7:156585476G>C; GRCh37/hg19) was detected in all affected family members. Functional characterization using a mouse transgenic enhancer essay showed extended ectopic expression dispersed throughout the entire limb bud (E11.5).ConclusionOur work describes the first mutation in the pZRS to be associated with TPT-PS and provides functional evidence that this mutation leads to ectopic expression of this enhancer within the developing limb.GENETICS in MEDICINE advance online publication, 15 March 2018; doi:10.1038/gim.2018.18.
			PMID: 29543231 DOI: 10.1038/gim.2018.18

	===The chick limb: embryology, genetics and teratology===		===The chick limb: embryology, genetics and teratology===

Z8600021 at 05:08, 16 July 2018

2018-07-16T05:08:01Z

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	<pubmed limit=5>Limb Development</pubmed>		<pubmed limit=5>Limb Development</pubmed>

			==2018==
			===The chick limb: embryology, genetics and teratology===

			Int J Dev Biol. 2018;62(1-2-3):85-95. doi: 10.1387/ijdb.170315CT.

			Davey MG1, Towers M, Vargesson N, Tickle C.
			Author information
			Abstract
			The chick embryo has a long history in investigations of vertebrate limb development because of the ease with which its limbs can be experimentally manipulated. Early studies elucidated the fundamental embryology of the limb and identified the key signalling regions that govern its development. The chick limb became a leading model for exploring the concept of positional information and understanding how patterns of differentiated cells and tissues develop in vertebrate embryos. When developmentally important molecules began to be identified, experiments in chick limbs were crucial for bridging embryology and molecular biology. The embryological mechanisms and molecular basis of limb development are largely conserved in mammals, including humans, and uncovering these molecular networks provides links to clinical genetics. We emphasise the important contributions of naturally occurring chick mutants to elucidating limb embryology and identifying novel developmentally important genes. In addition, we consider how the chick limb has been used to study mechanisms involved in teratogenesis with a focus on thalidomide. These studies on chick embryos have given insights into how limb defects can be caused by both genetic changes and chemical insults and therefore are of great medical significance.
			PMID: 29616743 DOI: 10.1387/ijdb.170315CT

	==2016==		==2016==

Z8600021 at 02:49, 13 September 2016

2016-09-13T02:49:20Z

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	==2015==		==2015==

			===RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud Induction and Initiation===

			Cell Rep. 2015 Aug 4;12(5):879-91. doi: 10.1016/j.celrep.2015.06.068. Epub 2015 Jul 23.

			Nishimoto S1, Wilde SM1, Wood S2, Logan MP3.

			Abstract

			The retinoic acid (RA)- and β-catenin-signaling pathways regulate limb bud induction and initiation; however, their mechanisms of action are not understood and have been disputed. We demonstrate that both pathways are essential and that RA and β-catenin/TCF/LEF signaling act cooperatively with Hox gene inputs to directly regulate Tbx5 expression. Furthermore, in contrast to previous models, we show that Tbx5 and Tbx4 expression in forelimb and hindlimb, respectively, are not sufficient for limb outgrowth and that input from RA is required. Collectively, our data indicate that RA signaling and Tbx genes act in a coherent feed-forward loop to regulate Fgf10 expression and, as a result, establish a positive feedback loop of FGF signaling between the limb mesenchyme and ectoderm. Our results incorporate RA-, β-catenin/TCF/LEF-, and FGF-signaling pathways into a regulatory network acting to recruit cells of the embryo flank to become limb precursors.
			Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

			PMID 26212321

	===Engrailed 1 mediates correct formation of limb innervation through two distinct mechanisms===		===Engrailed 1 mediates correct formation of limb innervation through two distinct mechanisms===

Z8600021 at 00:35, 20 August 2016

2016-08-20T00:35:22Z

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	==2016==		==2016==

			===Digits and fin rays share common developmental histories===

			Nakamura T, et al. Nature. 2016.


			Abstract

			Understanding the evolutionary transformation of fish fins into tetrapod limbs is a fundamental problem in biology. The search for antecedents of tetrapod digits in fish has remained controversial because the distal skeletons of limbs and fins differ structurally, developmentally, and histologically. Moreover, comparisons of fins with limbs have been limited by a relative paucity of data on the cellular and molecular processes underlying the development of the fin skeleton. Here, we provide a functional analysis, using CRISPR/Cas9 and fate mapping, of 5' hox genes and enhancers in zebrafish that are indispensable for the development of the wrists and digits of tetrapods. We show that cells marked by the activity of an autopodial hoxa13 enhancer exclusively form elements of the fin fold, including the osteoblasts of the dermal rays. In hox13 knockout fish, we find that a marked reduction and loss of fin rays is associated with an increased number of endochondral distal radials. These discoveries reveal a cellular and genetic connection between the fin rays of fish and the digits of tetrapods and suggest that digits originated via the transition of distal cellular fates.

			PMID 27533041


	===A somitic contribution to the apical ectodermal ridge is essential for fin formation===		===A somitic contribution to the apical ectodermal ridge is essential for fin formation===

Z8600021 at 02:12, 15 August 2016

2016-08-15T02:12:27Z

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	<pubmed limit=5>Limb Development</pubmed>		<pubmed limit=5>Limb Development</pubmed>

			==2016==

			===A somitic contribution to the apical ectodermal ridge is essential for fin formation===

			Nature. 2016 Jul 28;535(7613):542-6.

			Masselink W, Cole NJ, Fenyes F, Berger S, Sonntag C, Wood A, Nguyen PD, Cohen N, Knopf F, Weidinger G, Hall TE, Currie PD.

			Abstract
			The transition from fins to limbs was an important terrestrial adaptation, but how this crucial evolutionary shift arose developmentally is unknown. Current models focus on the distinct roles of the apical ectodermal ridge (AER) and the signaling molecules that it secretes during limb and fin outgrowth. In contrast to the limb AER, the AER of the fin rapidly transitions into the apical fold and in the process shuts off AER-derived signals that stimulate proliferation of the precursors of the appendicular skeleton. The differing fates of the AER during fish and tetrapod development have led to the speculation that fin-fold formation was one of the evolutionary hurdles to the AER-dependent expansion of the fin mesenchyme required to generate the increased appendicular structure evident within limbs. Consequently, a heterochronic shift in the AER-to-apical-fold transition has been postulated to be crucial for limb evolution. The ability to test this model has been hampered by a lack of understanding of the mechanisms controlling apical fold induction. Here we show that invasion by cells of a newly identified somite-derived lineage into the AER in zebrafish regulates apical fold induction. Ablation of these cells inhibits apical fold formation, prolongs AER activity and increases the amount of fin bud mesenchyme, suggesting that these cells could provide the timing mechanism proposed in Thorogood's clock model of the fin-to-limb transition. We further demonstrate that apical-fold inducing cells are progressively lost during gnathostome evolution;the absence of such cells within the tetrapod limb suggests that their loss may have been a necessary prelude to the attainment of limb-like structures in Devonian sarcopterygian fish.

			PMID 27437584

	==2015==		==2015==

Z8600021 at 11:08, 6 October 2015

2015-10-06T11:08:51Z

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	==2015==		==2015==

			===Engrailed 1 mediates correct formation of limb innervation through two distinct mechanisms===

			PLoS One. 2015 Feb 24;10(2):e0118505. doi: 10.1371/journal.pone.0118505. eCollection 2015.

			Huettl RE1, Luxenhofer G1, Bianchi E1, Haupt C2, Joshi R3, Prochiantz A3, Huber AB1.

			Abstract

			Engrailed-1 (En1) is expressed in the ventral ectoderm of the developing limb where it plays an instructive role in the dorsal-ventral patterning of the forelimb. Besides its well-described role as a transcription factor in regulating gene expression through its DNA-binding domain, En1 may also be secreted to form an extracellular gradient, and directly impact on the formation of the retinotectal map. We show here that absence of En1 causes mispatterning of the forelimb and thus defects in the dorsal-ventral pathfinding choice of motor axons in vivo. In addition, En1 but not En2 also has a direct and specific repulsive effect on motor axons of the lateral aspect of the lateral motor column (LMC) but not on medial LMC projections. Moreover, an ectopic dorsal source of En1 pushes lateral LMC axons to the ventral limb in vivo. Thus, En1 controls the establishment of limb innervation through two distinct molecular mechanisms.

			PMID 25710467

	===How the embryo makes a limb: determination, polarity and identity===		===How the embryo makes a limb: determination, polarity and identity===