Regulation of limb patterning by extracellular microfibrils

Emilio Arteaga-Solis, Barbara Gayraud, Sui Y. Lee, Lillian Shum, Lynn Sakai, Francesco Ramirez

Research output: Contribution to journalArticle

158 Citations (Scopus)

Abstract

To elucidate the contribution of the extracellular microfibril-elastic fiber network to vertebrate organogenesis, we generated fibrillin 2 (Fbn2)-null mice by gene targeting and identified a limb-patterning defect in the form of bilateral syndactyly. Digit fusion involves both soft and hard tissues, and is associated with reduced apoptosis at affected sites. Two lines of evidence suggest that syndactily is primarily due to defective mesenchyme differentiation, rather than reduced apoptosis of interdigital tissue. First, fusion occurs before appearance of interdigital cell death; second, interdigital tissues having incomplete separation fail to respond to apoptotic clues from implanted BMP-4 beads. Syndactyly is associated with a disorganized matrix, but with normal BMP gene expression. On the other hand, mice double heterozygous for null Fbn2 and Bmp7 alleles display the combined digit phenotype of both nullizygotes. Together, these results imply functional interaction between Fbn2-rich microfibrils and BMP-7 signaling. As such, they uncover an unexpected relationship between the insoluble matrix and soluble factors during limb patterning. We also demonstrate that the Fbn2-null mutation is allelic to the recessive shaker-with-syndactyly (sy) locus on chromosome 18.

Original languageEnglish (US)
Pages (from-to)275-281
Number of pages7
JournalJournal of Cell Biology
Volume154
Issue number2
DOIs
StatePublished - Jul 23 2001
Externally publishedYes

Fingerprint

Microfibrils
Syndactyly
Extremities
Bone Morphogenetic Protein 7
Apoptosis
Chromosomes, Human, Pair 18
Elastic Tissue
Gene Targeting
Organogenesis
Mesoderm
Vertebrates
Cell Death
Alleles
Phenotype
Gene Expression
Mutation
Fibrillin-2

Keywords

  • BMP
  • Fibrillin
  • Limb patterning
  • Morphogenesis
  • Syndactyly

ASJC Scopus subject areas

  • Cell Biology

Cite this

Arteaga-Solis, E., Gayraud, B., Lee, S. Y., Shum, L., Sakai, L., & Ramirez, F. (2001). Regulation of limb patterning by extracellular microfibrils. Journal of Cell Biology, 154(2), 275-281. https://doi.org/10.1083/jcb.200105046

Regulation of limb patterning by extracellular microfibrils. / Arteaga-Solis, Emilio; Gayraud, Barbara; Lee, Sui Y.; Shum, Lillian; Sakai, Lynn; Ramirez, Francesco.

In: Journal of Cell Biology, Vol. 154, No. 2, 23.07.2001, p. 275-281.

Research output: Contribution to journalArticle

Arteaga-Solis, E, Gayraud, B, Lee, SY, Shum, L, Sakai, L & Ramirez, F 2001, 'Regulation of limb patterning by extracellular microfibrils', Journal of Cell Biology, vol. 154, no. 2, pp. 275-281. https://doi.org/10.1083/jcb.200105046
Arteaga-Solis E, Gayraud B, Lee SY, Shum L, Sakai L, Ramirez F. Regulation of limb patterning by extracellular microfibrils. Journal of Cell Biology. 2001 Jul 23;154(2):275-281. https://doi.org/10.1083/jcb.200105046
Arteaga-Solis, Emilio ; Gayraud, Barbara ; Lee, Sui Y. ; Shum, Lillian ; Sakai, Lynn ; Ramirez, Francesco. / Regulation of limb patterning by extracellular microfibrils. In: Journal of Cell Biology. 2001 ; Vol. 154, No. 2. pp. 275-281.
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