Talk:Musculoskeletal System - Limb Development

2010

Tbx4 and tbx5 acting in connective tissue are required for limb muscle and tendon patterning

Hasson P, DeLaurier A, Bennett M, Grigorieva E, Naiche LA, Papaioannou VE, Mohun TJ, Logan MP. Dev Cell. 2010 Jan 19;18(1):148-56. PMID: 20152185

Ectodermal Wnt6 is an early negative regulator of limb chondrogenesis in the chicken embryo

Geetha-Loganathan P, Nimmagadda S, Christ B, Huang R, Scaal M. BMC Dev Biol. 2010 Mar 25;10:32. PMID: 20334703

http://www.ncbi.nlm.nih.gov/pubmed/20334703

BACKGROUND: Pattern formation of the limb skeleton is regulated by a complex interplay of signaling centers located in the ectodermal sheath and mesenchymal core of the limb anlagen, which results, in the forelimb, in the coordinate array of humerus, radius, ulna, carpals, metacarpals and digits. Much less understood is why skeletal elements form only in the central mesenchyme of the limb, whereas muscle anlagen develop in the peripheral mesenchyme ensheathing the chondrogenic center. Classical studies have suggested a role of the limb ectoderm as a negative regulator of limb chondrogenesis.

RESULTS: In this paper, we investigated the molecular nature of the inhibitory influence of the ectoderm on limb chondrogenesis in the avian embryo in vivo. We show that ectoderm ablation in the early limb bud leads to increased and ectopic expression of early chondrogenic marker genes like Sox9 and Collagen II, indicating that the limb ectoderm inhibits limb chondrogenesis at an early stage of the chondrogenic cascade. To investigate the molecular nature of the inhibitory influence of the ectoderm, we ectopically expressed Wnt6, which is presently the only known Wnt expressed throughout the avian limb ectoderm, and found that Wnt6 overexpression leads to reduced expression of the early chondrogenic marker genes Sox9 and Collagen II.

CONCLUSION: Our results suggest that the inhibitory influence of the ectoderm on limb chondrogenesis acts on an early stage of chondrogenesis upsteam of Sox9 and Collagen II. We identify Wnt6 as a candidate mediator of ectodermal chondrogenic inhibition in vivo. We propose a model of Wnt-mediated centripetal patterning of the limb by the surface ectoderm.

The role of spatially controlled cell proliferation in limb bud morphogenesis

Boehm B, Westerberg H, Lesnicar-Pucko G, Raja S, Rautschka M, Cotterell J, Swoger J, Sharpe J. PLoS Biol. 2010 Jul 13;8(7):e1000420. PMID: 20644711

<pubmed>20644711</pubmed>| PMC2903592 | PLoS

Citation: Boehm B, Westerberg H, Lesnicar-Pucko G, Raja S, Rautschka M, et al. (2010) The Role of Spatially Controlled Cell Proliferation in Limb Bud Morphogenesis. PLoS Biol 8(7): e1000420. doi:10.1371/journal.pbio.1000420

Copyright: © 2010 Boehm 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.

Limbs made to measure.

Kicheva A, Briscoe J. PLoS Biol. 2010 Jul 13;8(7):e1000421. No abstract available. http://www.ncbi.nlm.nih.gov/pubmed/20644713 PMID: 20644713

<pubmed>20644713</pubmed>| PMC2903596 | PLoS

Citation: Kicheva A, Briscoe J (2010) Limbs Made to Measure. PLoS Biol 8(7): e1000421. doi:10.1371/journal.pbio.1000421

Published: July 13, 2010

Copyright: © 2010 Kicheva, Briscoe. 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.

2007

Six proteins regulate the activation of Myf5 expression in embryonic mouse limbs

Giordani J, Bajard L, Demignon J, Daubas P, Buckingham M, Maire P. Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11310-5. Epub 2007 Jun 25. PMID: 17592144

Département de Génétique et Développement, Institut Cochin, Université Paris Descartes, Paris, France.

Abstract Myf5, a member of the myogenic regulatory factor family, plays a major role in determining myogenic cell fate at the onset of skeletal muscle formation in the embryo. Spatiotemporal control of its expression during development requires multiple enhancer elements spread over >100 kb at the Myf5 locus. Transcription in embryonic limbs is regulated by a 145-bp element located at -57.5 kb from the Myf5 gene. In the present study we show that Myf5 expression is severely impaired in the limb buds of Six1(-/-) and Six1(-/-)Six4(-/+) mouse mutants despite the presence of myogenic progenitor cells. The 145-bp regulatory element contains a sequence that binds Six1 and Six4 in electromobility shift assays in vitro and in chromatin immunoprecipitation assays with embryonic extracts. We further show that Six1 is able to transactivate a reporter gene under the control of this sequence. In vivo functionality of the Six binding site is demonstrated by transgenic analysis. Mutation of this site impairs reporter gene expression in the limbs and in mature somites where the 145-bp regulatory element is also active. Six1/4 therefore regulate Myf5 transcription, together with Pax3, which was previously shown to be required for the activity of the 145-bp element. Six homeoproteins, which also directly regulate the myogenic differentiation gene Myogenin and lie genetically upstream of Pax3, thus control hypaxial myogenesis at multiple levels.

PMID: 17592144

Hedgehog signaling regulates the amount of hypaxial muscle development during Xenopus myogenesis

Martin BL, Peyrot SM, Harland RM. Dev Biol. 2007 Apr 15;304(2):722-34. Epub 2007 Feb 7. PMID: 17320852

Eya1 and Eya2 proteins are required for hypaxial somitic myogenesis in the mouse embryo

Grifone R, Demignon J, Giordani J, Niro C, Souil E, Bertin F, Laclef C, Xu PX, Maire P. Dev Biol. 2007 Feb 15;302(2):602-16. Epub 2006 Sep 1. PMID: 17098221

Forelimb-hindlimb developmental timing changes across tetrapod phylogeny

BMC Evol Biol. 2007 Oct 1;7:182.

Bininda-Emonds OR, Jeffery JE, Sánchez-Villagra MR, Hanken J, Colbert M, Pieau C, Selwood L, Ten Cate C, Raynaud A, Osabutey CK, Richardson MK.

Institute of Biology, University of Leiden, Kaiserstraat 63, 2311GP, Leiden, The Netherlands. Olaf.Bininda@uni-jena.de

Abstract BACKGROUND: Tetrapods exhibit great diversity in limb structures among species and also between forelimbs and hindlimbs within species, diversity which frequently correlates with locomotor modes and life history. We aim to examine the potential relation of changes in developmental timing (heterochrony) to the origin of limb morphological diversity in an explicit comparative and quantitative framework. In particular, we studied the relative time sequence of development of the forelimbs versus the hindlimbs in 138 embryos of 14 tetrapod species spanning a diverse taxonomic, ecomorphological and life-history breadth. Whole-mounts and histological sections were used to code the appearance of 10 developmental events comprising landmarks of development from the early bud stage to late chondrogenesis in the forelimb and the corresponding serial homologues in the hindlimb.

RESULTS: An overall pattern of change across tetrapods can be discerned and appears to be relatively clade-specific. In the primitive condition, as seen in Chondrichthyes and Osteichthyes, the forelimb/pectoral fin develops earlier than the hindlimb/pelvic fin. This pattern is either retained or re-evolved in eulipotyphlan insectivores (= shrews, moles, hedgehogs, and solenodons) and taken to its extreme in marsupials. Although exceptions are known, the two anurans we examined reversed the pattern and displayed a significant advance in hindlimb development. All other species examined, including a bat with its greatly enlarged forelimbs modified as wings in the adult, showed near synchrony in the development of the fore and hindlimbs.

CONCLUSION: Major heterochronic changes in early limb development and chondrogenesis were absent within major clades except Lissamphibia, and their presence across vertebrate phylogeny are not easily correlated with adaptive phenomena related to morphological differences in the adult fore- and hindlimbs. The apparently conservative nature of this trait means that changes in chondrogenetic patterns may serve as useful phylogenetic characters at higher taxonomic levels in tetrapods. Our results highlight the more important role generally played by allometric heterochrony in this instance to shape adult morphology.

PMID: 17908305 http://www.biomedcentral.com/1471-2148/7/182

A two-step mechanism for myotome formation in chick

Dev Cell. 2004 Jun;6(6):875-82.

Gros J, Scaal M, Marcelle C.

Laboratoire de Génétique et Physiologie du Développement, Developmental Biology Institute of Marseille, CNRS/INSERM, Université de la Méditerranée, 13288 Marseille, France. Abstract The study of the morphogenetic cell movements underlying myotome formation in the chick embryo has led to the emergence of highly controversial models. Here we report a real-time cell lineage analysis of myotome development using electroporation of a GFP reporter in newly formed chick somites. Confocal analysis of cell movements demonstrates that myotome formation involves two sequential steps. In a first phase, incremental myotome growth results from a contribution of myocytes derived solely from the medial border of the dermomyotome. In a second phase, myocytes are produced from all four borders of the dermomyotome. The relative distribution of myocytes demonstrates that the medial and the lateral borders of the somite generate exclusively epaxial and hypaxial muscles. This analysis also identified five myotomal regions, characterized by the origin of the myocytes that constitute them. Together, our results provide a comprehensive model describing the morphogenesis of the early myotome in higher vertebrates.

PMID: 15177035