Yin and Yang in BMP signaling: Impact on the pathology of diseases and potential for tissue regeneration

Hartung, Anke; Sieber, Christina; Knaus, Petra

doi:10.1002/sita.200600098

Cited by 14 publications

(14 citation statements)

References 159 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phosphorylated Smads associate with the common co-factor Smad4, translocate to the nucleus and activate the transcription of target genes. BMP/Gdf signaling is fine-tuned at several levels, for example by secreted antagonists that interfere with ligand-receptor binding, such as Noggin (NOG; reviewed e.g., in Hoffmann and Gross, 2001;Hartung et al, 2006). Sox9 is a major target of BMP signaling in chondrogenesis (Healy et al, 1999;Zehentner et al, 1999;Pan et al, 2008Pan et al, , 2009).…”

Section: Condensation Of the Digit Anlagenmentioning

confidence: 99%

Mechanisms of digit formation: Human malformation syndromes tell the story

Stricker

Mundlos

2011

Developmental Dynamics

View full text Add to dashboard Cite

Identifying the genetic basis of human limb malformation disorders has been instrumental in improving our understanding of limb development. Abnormalities of the hands and/or feet include defects affecting patterning, establishment, elongation, and segmentation of cartilaginous condensations, as well as growth of the individual skeletal elements. While the phenotype of such malformations is highly diverse, the mutations identified to date cluster in genes implicated in a limited number of molecular pathways, namely hedgehog, Wnt, and bone morphogenetic protein. The latter pathway appears to function as a key molecular network regulating different phases of digit and joint development. Studies in animal models not only extended our insight into the pathogenesis of these conditions, but have also contributed to our understanding of the in vivo functions and interactions of these key players. This review is aimed at integrating the current understanding of human digit malformations into the increasing knowledge of the molecular mechanisms of digit development. Developmental Dynamics 240:990-1004,

show abstract

Section: Condensation Of the Digit Anlagenmentioning

confidence: 99%

Mechanisms of digit formation: Human malformation syndromes tell the story

Stricker

Mundlos

2011

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…Both type I and type II BMP receptors are serine/threonine kinases that have similar functional domains. Ligand binding occurs preferentially at the N‐terminal extracellular domain of the BMP type I receptor, which is connected by a single transmembrane region to the C‐terminal cytoplasmic kinase domain 40–43 . A unique feature of type I receptors is a cytoplasmic juxtamembrane region rich in glycine and serine residues (GS domain).…”

Section: Morphogen Receptor Genes and Metamorphogenesmentioning

confidence: 99%

“…BMP signaling can be mediated by four known type I receptors: TSR (ALK1); ACVR1 (ALK2); BMPR1A (ALK3); and BMPR1B (ALK6). Numerous comprehensive reviews are available on this seminal signaling pathway that will orient the reader to the concepts that follow 40–43 …”

Section: Morphogen Receptor Genes and Metamorphogenesmentioning

confidence: 99%

Morphogen Receptor Genes and Metamorphogenes

Kaplan

Groppe

Pignolo

et al. 2007

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

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.

show abstract

“…BMP gene mutations show positive linkages to different clinical syndromes (Hartung et al, 2006). For example, Luyten showed that mutations in cartilage-derived morphogenetic protein 1 (CDMP1), which is also known as growth-differentiation factor 5 (GDF5), are implicated in two recessive chondrodysplasias: the Hunter-Thompson type and the Grebe type (Thomas et al, 1997).…”

Section: Skeletal Diseasesmentioning

confidence: 99%