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The atypical homeodomain transcription factor Mohawk controls tendon morphogenesis.

The Mohawk homeobox (Mkx) gene encodes a new atypical homeodomain-containing protein with transcriptional repressor activity. Mkx mRNA exhibited dynamic expression patterns during development of the palate, somite, kidney, and testis, suggesting that it may be an important regulator of multiple developmental processes. To investigate the roles of Mkx in organogenesis, we generated mice carrying a null mutation in this gene. Mkx(-/-) mice survive postnatally and exhibit a unique wavy-tail phenotype. Close examination revealed that the mutant mice had smaller tendons than wild-type littermates and that the rapid postnatal growth of collagen fibrils in tendons was disrupted in Mkx(-/-) mice. Defects in tendon development were detected in the mutant mouse embryos as early as embryonic day 16.5 (E16.5). Although collagen fibril assembly initially appeared normal, the tendons of Mkx(-/-) embryos expressed significantly reduced amounts of collagen I, fibromodulin, and tenomodulin in comparison with control littermates. We found that Mkx mRNA was strongly expressed in differentiating tendon cells during embryogenesis and in the tendon sheath cells in postnatal stages. In addition to defects in tendon collagen fibrillogenesis, Mkx(-/-) mutant mice exhibited abnormal tendon sheaths. These results identify Mkx as an important regulator of tendon development.

Pubmed ID: 20696843

Authors

  • Liu W
  • Watson SS
  • Lan Y
  • Keene DR
  • Ovitt CE
  • Liu H
  • Schweitzer R
  • Jiang R

Journal

Molecular and cellular biology

Publication Data

October 23, 2010

Associated Grants

  • Agency: NIAMS NIH HHS, Id: AR055640
  • Agency: NIDCR NIH HHS, Id: DE013681
  • Agency: NIDCR NIH HHS, Id: DE015207
  • Agency: NIDCR NIH HHS, Id: R01 DE013681
  • Agency: NIDCR NIH HHS, Id: R01 DE015207

Mesh Terms

  • Animals
  • Base Sequence
  • DNA Primers
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Knockout Techniques
  • Homeodomain Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • Morphogenesis
  • Phenotype
  • Pregnancy
  • RNA, Messenger
  • Tendons