Talk:Musculoskeletal System - Limb Development: Difference between revisions
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PMID: 21383175 | PMID: 21383175 | ||
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==2010== | ==2010== | ||
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Cite this page: Hill, M.A. (2024, April 27) Embryology Musculoskeletal System - Limb Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Musculoskeletal_System_-_Limb_Development |
2011
Axial Hox9 activity establishes the posterior field in the developing forelimb
Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4888-91. Epub 2011 Mar 7.
Xu B, Wellik DM.
Department of Internal Medicine, Division of Molecular Medicine and Genetics and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-2200.
Abstract
Current models hold that the early limb field becomes polarized into anterior and posterior domains by the opposing activities of Hand2 and Gli3. This polarization is essential for the initiation of Shh expression in the posterior margin of the limb bud, but how this polarity is established is not clear. Here we show that initial anteroposterior polarization of the early forelimb field requires the function of all four Hox9 paralogs (Hoxa9, Hoxb9, Hoxc9, and Hoxd9). This is unexpected, given that only HoxA and HoxD AbdB group genes have been shown to play a role in forelimb patterning, regulating the activation and maintenance of Shh expression and subsequent proximal-distal patterning of the forelimb. Our analysis of Hox9 quadruple mutants demonstrates that Hox9 function is required for the expression of Hand2 in the posterior limb field. Subsequently, Gli3 expression is not repressed posteriorly, Shh expression is not initiated, and collinear expression of HoxA/D10-13 is not established, resulting in severely malformed forelimbs lacking all posterior, Shh-regulated elements. This Hox9 mutant phenotype is restricted to the forelimbs; mutant hindlimbs are normal, revealing fundamental differences in the patterning mechanisms governing the establishment of forelimb and hindlimb fields.
PMID: 21383175 http://www.ncbi.nlm.nih.gov/pubmed/21383175
http://www.pnas.org/content/108/12/4888.long
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
Genetic evidence that SOST inhibits WNT signaling in the limb
Dev Biol. 2010 Jun 15;342(2):169-79. Epub 2010 Mar 30.
Collette NM, Genetos DC, Murugesh D, Harland RM, Loots GG.
Biology and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.
Abstract SOST is a negative regulator of bone formation, and mutations in human SOST are responsible for sclerosteosis. In addition to high bone mass, sclerosteosis patients occasionally display hand defects, suggesting that SOST may function embryonically. Here we report that overexpression of SOST leads to loss of posterior structures of the zeugopod and autopod by perturbing anterior-posterior and proximal-distal signaling centers in the developing limb. Mutant mice that overexpress SOST in combination with Grem1 and Lrp6 mutations display more severe limb defects than single mutants alone, while Sost(-/-) significantly rescues the Lrp6(-/-) skeletal phenotype, signifying that SOST gain-of-function impairs limb patterning by inhibiting the WNT signaling through LRP5/6.
- "Our findings are also consistent with recent reports that BMP signaling negatively regulates bone mass by induction of sclerostin which then inhibits the canonical WNT pathway (Kamiya et al., 2008)."
Copyright 2010 Elsevier Inc. All rights reserved.
PMID: 20359476
http://www.ncbi.nlm.nih.gov/pubmed/20359476
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
EMBL-CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), UPF, Barcelona, Spain.
Abstract
Although the vertebrate limb bud has been studied for decades as a model system for spatial pattern formation and cell specification, the cellular basis of its distally oriented elongation has been a relatively neglected topic by comparison. The conventional view is that a gradient of isotropic proliferation exists along the limb, with high proliferation rates at the distal tip and lower rates towards the body, and that this gradient is the driving force behind outgrowth. Here we test this hypothesis by combining quantitative empirical data sets with computer modelling to assess the potential role of spatially controlled proliferation rates in the process of directional limb bud outgrowth. In particular, we generate two new empirical data sets for the mouse hind limb--a numerical description of shape change and a quantitative 3D map of cell cycle times--and combine these with a new 3D finite element model of tissue growth. By developing a parameter optimization approach (which explores spatial patterns of tissue growth) our computer simulations reveal that the observed distribution of proliferation rates plays no significant role in controlling the distally extending limb shape, and suggests that directional cell activities are likely to be the driving force behind limb bud outgrowth. This theoretical prediction prompted us to search for evidence of directional cell orientations in the limb bud mesenchyme, and we thus discovered a striking highly branched and extended cell shape composed of dynamically extending and retracting filopodia, a distally oriented bias in Golgi position, and also a bias in the orientation of cell division. We therefore provide both theoretical and empirical evidence that limb bud elongation is achieved by directional cell activities, rather than a PD gradient of proliferation rates.
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.
The temporal dynamics of vertebrate limb development, teratogenesis and evolution
Curr Opin Genet Dev. 2010 Aug;20(4):384-90. Epub 2010 May 27.
Zeller R.
Developmental Genetics, Department of Biomedicine, University of Basel Medical Faculty, Mattenstrasse 28, Basel, Switzerland. Rolf.Zeller@unibas.ch Abstract Recent genetic and functional analysis of vertebrate limb development begins to reveal how the functions of particular genes and regulatory hierarchies can drastically change over time. The temporal and spatial interplay of the two instructive signalling centres are part of a larger signalling system that orchestrates limb bud morphogenesis in a rather self-regulatory manner. It appears that mesenchymal cells are specified early and subsequently, the progenitors for the different skeletal elements are expanded and determined progressively during outgrowth. Mutations and teratogens that disrupt distal progression of limb development most often cause death of the early-specified progenitors rather than altering their fates. The proliferative expansion and distal progression of paired appendage development was one of the main driving forces behind the transition from fin to limb buds during paired appendage evolution. Finally, the adaptive diversification or loss of modern tetrapod limbs in particular phyla or species appear to be a consequence of evolutionary tampering with the regulatory systems that control distal progression of limb development.
PMID: 20537528 http://www.ncbi.nlm.nih.gov/pubmed/20537528
2008
Avian pelvis originates from lateral plate mesoderm and its development requires signals from both ectoderm and paraxial mesoderm
Cell Tissue Res. 2008 Mar;331(3):595-604. Epub 2007 Dec 18.
Malashichev Y, Christ B, Pröls F.
Department of Vertebrate Zoology, Faculty of Biology and Soil Sciences, St Petersburg State University, Universitetskaya nab, St Petersburg, Russia. malashichev@gmail.com Abstract The pelvic girdle is composed of three skeletal elements: ilium, pubis, and ischium. In comparison with other parts of the postcranial skeleton, its development is not well known to date. To elucidate the embryonic origin of the avian pelvic girdle and the signaling centers that control its development, we have performed extirpation and quail-to-chick grafting experiments. The results reveal that the entire pelvic girdle originates from the somatopleure at somite levels 26 to 35. No somitic cell contribution to skeletal elements of the pelvis has been detected. Removal of the surface ectoderm covering the lateral plate mesoderm has revealed that ectodermal signals control the development of the pelvic girdle, especially the formation of the pubis and ischium. The impaired development of the ischium and pubis correlates with the downregulation of Pax1 and Alx4, two transcription factors that control the normal development of the ischium and pubis. Although of somatopleural origin, the development of the ilium depends on somitic signals. Insertion of a barrier between somites and somatopleure disrupts the expression of Emx2 and prevents normal development of the ilium but does not affect the expression of Pax1 or Alx4 and the development of the pubis and ischium. Thus, the development of the ilium, but not of the pubis and ischium, depends on somitic and ectodermal signals.
PMID: 18087724 http://www.ncbi.nlm.nih.gov/pubmed/18087724
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
2004
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
2001
Developmental mechanisms of vertebrate limb evolution
Novartis Found Symp. 2001;232:47-57; discussion 57-62.
Cohn MJ.
Division of Zoology, School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading RG6 6AJ, UK. Abstract Over the past few years, our understanding of the evolution of limbs has been improved by important new discoveries in the fossil record. Additionally, rapid progress has been made in identifying the molecular basis of vertebrate limb development. It is now possible to integrate these two areas of research in order to identify the molecular developmental mechanisms underlying the evolution of paired appendages in vertebrates. After the origin of paired appendages, several vertebrate lineages reduced or eliminated fins and limbs and returned to the limbless condition. Examples include eels, caecilians, snakes, slow worms and several marine mammals. Analyses of fossil and extant vertebrates show that evolution of limblessness frequently occurred together with elongation of the trunk and loss of clear morphological boundaries in the vertebral column. This may be suggestive of a common developmental mechanism linking these two processes. We have addressed this question by analysing python embryonic development at tissue, cellular and molecular levels, and we have identified a developmental mechanism which may account for evolution of limb loss in these animals.
PMID: 11277086 http://www.ncbi.nlm.nih.gov/pubmed/11277086
Development and evolution of the mammalian limb: adaptive diversification of nails, hooves, and claws
Evol Dev. 2001 Sep-Oct;3(5):355-63.
Hamrick MW.
Department of Anthropology & School of Biomedical Sciences, Kent State University, OH 44242, USA. mhamrick@kent.edu Abstract Paleontological evidence indicates that the evolutionary diversification of mammals early in the Cenozoic era was characterized by an adaptive radiation of distal limb structures. Likewise, neontological data show that morphological variation in distal limb integumentary appendages (e.g., nails, hooves, and claws) can be observed not only among distantly related mammalian taxa but also among closely related species within the same clade. Comparative analysis of nail, claw, and hoof morphogenesis reveals relatively subtle differences in mesenchymal and epithelial patterning underlying these adult differences in distal limb appendage morphology. Furthermore, studies of regulatory gene expression during vertebrate claw development demonstrate that many of the signaling molecules involved in patterning ectodermal derivatives such as teeth, hair, and feathers are also involved in organizing mammalian distal limb appendages. For example, Bmp4 signaling plays an important role during the recruitment of mesenchymal cells into the condensations forming the terminal phalanges, whereas Msx2 affects the length of nails and claws by suppressing proliferation of germinal epidermal cells. Evolutionary changes in the form of distal integumentary appendages may therefore result from changes in gene expression during formation of mesenchymal condensations (Bmp4, posterior Hox genes), induction of the claw fold and germinal matrix (shh), and/or proliferation of epidermal cells in the claw matrix (Msx1, Msx2). The prevalence of convergences and parallelisms in nail and claw structure among mammals underscores the existence of multiple morphogenetic pathways for evolutionary change in distal limb appendages.
PMID: 11710767 http://www.ncbi.nlm.nih.gov/pubmed/11710767
1997
Fossils, genes and the evolution of animal limbs
Nature. 1997 Aug 14;388(6643):639-48.
Shubin N, Tabin C, Carroll S.
Department of Biology, University of Pennsylvania, Philadelphia 19104, USA. nshubin@sas.upenn.edu Abstract The morphological and functional evolution of appendages has played a crucial role in the adaptive radiation of tetrapods, arthropods and winged insects. The origin and diversification of fins, wings and other structures, long a focus of palaeontology, can now be approached through developmental genetics. Modifications of appendage number and architecture in each phylum are correlated with regulatory changes in specific patterning genes. Although their respective evolutionary histories are unique, vertebrate, insect and other animal appendages are organized by a similar genetic regulatory system that may have been established in a common ancestor.
PMID: 9262397 http://www.ncbi.nlm.nih.gov/pubmed/9262397
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imaging - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2878749/?tool=pubmed
