Morphogen receptor genes and metamorphogenes

Skeleton keys to metamorphosis

Frederick S. Kaplan, Jay Groppe, Robert Pignolo, Eileen M. Shore

Research output: Chapter in Book/Report/Conference proceedingConference contribution

29 Citations (Scopus)

Abstract

Morphogen receptors are nodal points in signal transduction pathways that regulate morphogenesis during embryonic development. A recent discovery identified a recurrent missense mutation in a gene encoding a morphogen receptor responsible for the elusive process of skeletal metamorphosis in humans. Metamorphosis, the postnatal transformation of one normal tissue or organ system into another, is a biological process rarely seen in higher vertebrates or mammals, but exemplified pathologically by the disabling autosomal dominant disorder, fibrodysplasia ossificans progressiva (FOP). Individuals with FOP experience episodes of spontaneous or trauma-induced metamorphosis that convert normal functioning aponeuroses, fascia, ligaments, tendons, and skeletal muscles into a highly ramified and disabling second skeleton of heterotopic bone. The recurrent single nucleotide missense mutation in the gene encoding activin receptor IA/activin-like kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor that causes FOP in all classically affected individuals worldwide, is one of the most specific disease-causing mutations in the human genome and the first identified human metamorphogene. These findings provide deep insight into a signaling pathway that regulates tissue and organ stability following morphogenesis, and that when dysregulated in a specific manner, orchestrates the metamorphosis of one normal tissue or organ system into another. The study of skeletal metamorphosis in FOP provides profound insight into the molecular mechanisms that ensure phenotypic stability following morphogenesis and that ordinarily lay deeply hidden in the highly conserved signaling pathways that regulate cell fate. Such insight is applicable to a broad range of human afflictions.

Original languageEnglish (US)
Title of host publicationSkeletal Biology and Medicine, Part A
Subtitle of host publicationAspects of Bone Morphogenesis and Remodeling
PublisherBlackwell Publishing Inc.
Pages113-133
Number of pages21
ISBN (Print)9781573316842
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1116
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Fingerprint

Myositis Ossificans
Skeleton
Gene encoding
Genes
Morphogenesis
Tissue
Type I Bone Morphogenetic Protein Receptors
Missense Mutation
Activin Receptors
Activins
Signal transduction
Mammals
Ligaments
Tendons
Biological Phenomena
Muscle
Fascia
Bone
Human Genome
Phosphotransferases

Keywords

  • ACVR1
  • BMP
  • BMP receptor
  • BMP signaling pathways
  • Bone morphogenetic protein
  • Fibrodysplasia ossificans progressiva
  • Heterotopic ossification
  • Metamorphogene
  • Metamorphosis
  • Morphogen
  • Morphogen receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Kaplan, F. S., Groppe, J., Pignolo, R., & Shore, E. M. (2007). Morphogen receptor genes and metamorphogenes: Skeleton keys to metamorphosis. In Skeletal Biology and Medicine, Part A: Aspects of Bone Morphogenesis and Remodeling (pp. 113-133). (Annals of the New York Academy of Sciences; Vol. 1116). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1402.039

Morphogen receptor genes and metamorphogenes : Skeleton keys to metamorphosis. / Kaplan, Frederick S.; Groppe, Jay; Pignolo, Robert; Shore, Eileen M.

Skeletal Biology and Medicine, Part A: Aspects of Bone Morphogenesis and Remodeling. Blackwell Publishing Inc., 2007. p. 113-133 (Annals of the New York Academy of Sciences; Vol. 1116).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Kaplan, FS, Groppe, J, Pignolo, R & Shore, EM 2007, Morphogen receptor genes and metamorphogenes: Skeleton keys to metamorphosis. in Skeletal Biology and Medicine, Part A: Aspects of Bone Morphogenesis and Remodeling. Annals of the New York Academy of Sciences, vol. 1116, Blackwell Publishing Inc., pp. 113-133. https://doi.org/10.1196/annals.1402.039
Kaplan FS, Groppe J, Pignolo R, Shore EM. Morphogen receptor genes and metamorphogenes: Skeleton keys to metamorphosis. In Skeletal Biology and Medicine, Part A: Aspects of Bone Morphogenesis and Remodeling. Blackwell Publishing Inc. 2007. p. 113-133. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1402.039
Kaplan, Frederick S. ; Groppe, Jay ; Pignolo, Robert ; Shore, Eileen M. / Morphogen receptor genes and metamorphogenes : Skeleton keys to metamorphosis. Skeletal Biology and Medicine, Part A: Aspects of Bone Morphogenesis and Remodeling. Blackwell Publishing Inc., 2007. pp. 113-133 (Annals of the New York Academy of Sciences).
@inproceedings{a1060541fc10498789f8c4afa75b425f,
title = "Morphogen receptor genes and metamorphogenes: Skeleton keys to metamorphosis",
abstract = "Morphogen receptors are nodal points in signal transduction pathways that regulate morphogenesis during embryonic development. A recent discovery identified a recurrent missense mutation in a gene encoding a morphogen receptor responsible for the elusive process of skeletal metamorphosis in humans. Metamorphosis, the postnatal transformation of one normal tissue or organ system into another, is a biological process rarely seen in higher vertebrates or mammals, but exemplified pathologically by the disabling autosomal dominant disorder, fibrodysplasia ossificans progressiva (FOP). Individuals with FOP experience episodes of spontaneous or trauma-induced metamorphosis that convert normal functioning aponeuroses, fascia, ligaments, tendons, and skeletal muscles into a highly ramified and disabling second skeleton of heterotopic bone. The recurrent single nucleotide missense mutation in the gene encoding activin receptor IA/activin-like kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor that causes FOP in all classically affected individuals worldwide, is one of the most specific disease-causing mutations in the human genome and the first identified human metamorphogene. These findings provide deep insight into a signaling pathway that regulates tissue and organ stability following morphogenesis, and that when dysregulated in a specific manner, orchestrates the metamorphosis of one normal tissue or organ system into another. The study of skeletal metamorphosis in FOP provides profound insight into the molecular mechanisms that ensure phenotypic stability following morphogenesis and that ordinarily lay deeply hidden in the highly conserved signaling pathways that regulate cell fate. Such insight is applicable to a broad range of human afflictions.",
keywords = "ACVR1, BMP, BMP receptor, BMP signaling pathways, Bone morphogenetic protein, Fibrodysplasia ossificans progressiva, Heterotopic ossification, Metamorphogene, Metamorphosis, Morphogen, Morphogen receptor",
author = "Kaplan, {Frederick S.} and Jay Groppe and Robert Pignolo and Shore, {Eileen M.}",
year = "2007",
month = "1",
day = "1",
doi = "10.1196/annals.1402.039",
language = "English (US)",
isbn = "9781573316842",
series = "Annals of the New York Academy of Sciences",
publisher = "Blackwell Publishing Inc.",
pages = "113--133",
booktitle = "Skeletal Biology and Medicine, Part A",

}

TY - GEN

T1 - Morphogen receptor genes and metamorphogenes

T2 - Skeleton keys to metamorphosis

AU - Kaplan, Frederick S.

AU - Groppe, Jay

AU - Pignolo, Robert

AU - Shore, Eileen M.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - Morphogen receptors are nodal points in signal transduction pathways that regulate morphogenesis during embryonic development. A recent discovery identified a recurrent missense mutation in a gene encoding a morphogen receptor responsible for the elusive process of skeletal metamorphosis in humans. Metamorphosis, the postnatal transformation of one normal tissue or organ system into another, is a biological process rarely seen in higher vertebrates or mammals, but exemplified pathologically by the disabling autosomal dominant disorder, fibrodysplasia ossificans progressiva (FOP). Individuals with FOP experience episodes of spontaneous or trauma-induced metamorphosis that convert normal functioning aponeuroses, fascia, ligaments, tendons, and skeletal muscles into a highly ramified and disabling second skeleton of heterotopic bone. The recurrent single nucleotide missense mutation in the gene encoding activin receptor IA/activin-like kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor that causes FOP in all classically affected individuals worldwide, is one of the most specific disease-causing mutations in the human genome and the first identified human metamorphogene. These findings provide deep insight into a signaling pathway that regulates tissue and organ stability following morphogenesis, and that when dysregulated in a specific manner, orchestrates the metamorphosis of one normal tissue or organ system into another. The study of skeletal metamorphosis in FOP provides profound insight into the molecular mechanisms that ensure phenotypic stability following morphogenesis and that ordinarily lay deeply hidden in the highly conserved signaling pathways that regulate cell fate. Such insight is applicable to a broad range of human afflictions.

AB - Morphogen receptors are nodal points in signal transduction pathways that regulate morphogenesis during embryonic development. A recent discovery identified a recurrent missense mutation in a gene encoding a morphogen receptor responsible for the elusive process of skeletal metamorphosis in humans. Metamorphosis, the postnatal transformation of one normal tissue or organ system into another, is a biological process rarely seen in higher vertebrates or mammals, but exemplified pathologically by the disabling autosomal dominant disorder, fibrodysplasia ossificans progressiva (FOP). Individuals with FOP experience episodes of spontaneous or trauma-induced metamorphosis that convert normal functioning aponeuroses, fascia, ligaments, tendons, and skeletal muscles into a highly ramified and disabling second skeleton of heterotopic bone. The recurrent single nucleotide missense mutation in the gene encoding activin receptor IA/activin-like kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor that causes FOP in all classically affected individuals worldwide, is one of the most specific disease-causing mutations in the human genome and the first identified human metamorphogene. These findings provide deep insight into a signaling pathway that regulates tissue and organ stability following morphogenesis, and that when dysregulated in a specific manner, orchestrates the metamorphosis of one normal tissue or organ system into another. The study of skeletal metamorphosis in FOP provides profound insight into the molecular mechanisms that ensure phenotypic stability following morphogenesis and that ordinarily lay deeply hidden in the highly conserved signaling pathways that regulate cell fate. Such insight is applicable to a broad range of human afflictions.

KW - ACVR1

KW - BMP

KW - BMP receptor

KW - BMP signaling pathways

KW - Bone morphogenetic protein

KW - Fibrodysplasia ossificans progressiva

KW - Heterotopic ossification

KW - Metamorphogene

KW - Metamorphosis

KW - Morphogen

KW - Morphogen receptor

UR - http://www.scopus.com/inward/record.url?scp=37249082497&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37249082497&partnerID=8YFLogxK

U2 - 10.1196/annals.1402.039

DO - 10.1196/annals.1402.039

M3 - Conference contribution

SN - 9781573316842

T3 - Annals of the New York Academy of Sciences

SP - 113

EP - 133

BT - Skeletal Biology and Medicine, Part A

PB - Blackwell Publishing Inc.

ER -