AP-2β is a transcriptional regulator for determination of digit length in tetrapods

Ryohei Seki, Keiichi Kitajima, Haruka Matsubara, Takayuki Suzuki, Daisuke Saito, Hitoshi Yokoyama, Koji Tamura

研究成果: Article

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The species-specific morphology of digits in the tetrapod limb, including the length and number of metacarpal, metatarsal, and phalangeal bones, suggests that a common developmental mechanism for digit formation is modified in a species-specific manner. Here, we examined the function of the AP-2β transcription factor in regulating digit length in the chicken autopod. Mutations in the gene encoding AP-2β are associated with Char syndrome, a human autosomal dominant disorder. Char syndrome patients exhibit autopod skeletal defects, including loss of phalanges and shortened fingers, suggestive of a function for AP-2β in normal digit development. The ectopic expression of two different dominant-negative forms of chick AP-2β, equivalent to mutant forms associated with human Char syndrome, in the developing chick hindlimb bud resulted in defective digit formation, including reductions in the number and length of phalanges and metatarsals. A detailed analysis of the AP-2β expression pattern in the limb bud indicated a correlation between the pattern/duration of AP-2β expression in the limb mesenchyme and digit length in three amniote species, the chicken, mouse and gecko. In addition, we found that AP-2β expression was downstream of Fgf signals from the apical ectodermal ridge, which is crucial in digit morphogenesis, and that excessive AP-2β function resulted in dysregulated digit length. Taken together, these results suggest that AP-2β functions as a novel transcriptional regulator for digit morphogenesis.

元の言語English
ページ(範囲)75-89
ページ数15
ジャーナルDevelopmental Biology
407
発行部数1
DOI
出版物ステータスPublished - 2015 11 1

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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