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Book Chapter: Mechanistic insights into skeletal development gained from genetic disorders

TitleMechanistic insights into skeletal development gained from genetic disorders
Authors
KeywordsSkeletal disorders
Gene regulation
Genome folding
Limb patterning
Chondrocyte differentiation
Issue Date2019
PublisherAcademic Press
Citation
Mechanistic insights into skeletal development gained from genetic disorders. In Olsen, BR (Ed.), Current Topics in Developmental Biology, v. 133, p. 343-385. United States: Academic Press, 2019 How to Cite?
AbstractA complex cascade of highly regulated processes of cell fate determination, differentiation, proliferation and transdifferentiation dictate the patterning, morphogenesis and growth of the vertebrate skeleton, perturbation of which results in malformation. In humans over 450 different dysplasias involving the skeletal system constitute a significant fraction of documented Mendelian disorders. The combination of clinical, phenotypic characterization of rare human skeletal dysmorphologies, the discovery of causative mutations and functional validation in animal models has contributed enormously to the understanding of molecular control of skeletal development. These studies revealed a myriad of genes and pathways, such as WNT, Hedgehog (HH), planar cell polarity and primary cilia, as key regulators for skeletal patterning, growth and homeostasis. The generation of mouse models recapitulating human congenital skeletal dysplasia has provided mechanistic insights into the diverse pathologies caused by single gene mutations, integrated action of developmental pathways such as WNT and HH and the role of stress responses. Technological developments in whole genome and exome sequencing have accelerated the discovery of disease-causing mutations and are changing approaches for diagnosis. The discovery that non-coding variants and disorganization of the 3D genome are associated with limb patterning disorders has revealed an additional level of complexity in the regulatory framework of skeletal development and disease mechanisms. This chapter focuses on a selection of human skeletal pathologies which illustrate how new findings about the coding and noncoding genome, combined with functional modeling, are contributing to deeper understanding of skeletal development, mechanisms of disease, with therapeutic potential for chondrodysplasias.
DescriptionChapter Twelve
Persistent Identifierhttp://hdl.handle.net/10722/277342
ISBN
ISSN
2017 Impact Factor: 3.11
2015 SCImago Journal Rankings: 3.758

 

DC FieldValueLanguage
dc.contributor.authorYip, RKH-
dc.contributor.authorChan, D-
dc.contributor.authorCheah, KSE-
dc.date.accessioned2019-09-20T08:49:09Z-
dc.date.available2019-09-20T08:49:09Z-
dc.date.issued2019-
dc.identifier.citationMechanistic insights into skeletal development gained from genetic disorders. In Olsen, BR (Ed.), Current Topics in Developmental Biology, v. 133, p. 343-385. United States: Academic Press, 2019-
dc.identifier.isbn9780128104873-
dc.identifier.issn0070-2153-
dc.identifier.urihttp://hdl.handle.net/10722/277342-
dc.descriptionChapter Twelve-
dc.description.abstractA complex cascade of highly regulated processes of cell fate determination, differentiation, proliferation and transdifferentiation dictate the patterning, morphogenesis and growth of the vertebrate skeleton, perturbation of which results in malformation. In humans over 450 different dysplasias involving the skeletal system constitute a significant fraction of documented Mendelian disorders. The combination of clinical, phenotypic characterization of rare human skeletal dysmorphologies, the discovery of causative mutations and functional validation in animal models has contributed enormously to the understanding of molecular control of skeletal development. These studies revealed a myriad of genes and pathways, such as WNT, Hedgehog (HH), planar cell polarity and primary cilia, as key regulators for skeletal patterning, growth and homeostasis. The generation of mouse models recapitulating human congenital skeletal dysplasia has provided mechanistic insights into the diverse pathologies caused by single gene mutations, integrated action of developmental pathways such as WNT and HH and the role of stress responses. Technological developments in whole genome and exome sequencing have accelerated the discovery of disease-causing mutations and are changing approaches for diagnosis. The discovery that non-coding variants and disorganization of the 3D genome are associated with limb patterning disorders has revealed an additional level of complexity in the regulatory framework of skeletal development and disease mechanisms. This chapter focuses on a selection of human skeletal pathologies which illustrate how new findings about the coding and noncoding genome, combined with functional modeling, are contributing to deeper understanding of skeletal development, mechanisms of disease, with therapeutic potential for chondrodysplasias.-
dc.languageeng-
dc.publisherAcademic Press-
dc.relation.ispartofCurrent Topics in Developmental Biology-
dc.subjectSkeletal disorders-
dc.subjectGene regulation-
dc.subjectGenome folding-
dc.subjectLimb patterning-
dc.subjectChondrocyte differentiation-
dc.titleMechanistic insights into skeletal development gained from genetic disorders-
dc.typeBook_Chapter-
dc.identifier.emailChan, D: chand@hku.hk-
dc.identifier.emailCheah, KSE: hrmbdkc@hku.hk-
dc.identifier.authorityChan, D=rp00540-
dc.identifier.authorityCheah, KSE=rp00342-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/bs.ctdb.2019.02.002-
dc.identifier.pmid30902258-
dc.identifier.scopuseid_2-s2.0-85062327304-
dc.identifier.hkuros305908-
dc.identifier.volume133-
dc.identifier.spage343-
dc.identifier.epage385-
dc.publisher.placeUnited States-

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