AP-2β is a transcriptional regulator for determination of digit length in tetrapods.
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.
Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama Aoba-ku, Sendai 980-8578, Japan; Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
Ryohei
R
Seki
Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama Aoba-ku, Sendai 980-8578, Japan.
Keiichi
K
Kitajima
Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama Aoba-ku, Sendai 980-8578, Japan.
Haruka
H
Matsubara
Division of Biological Science, Guraduate School of Science, Nagoya University, Furo-Cho, Chikusa-ku, Nagoya 464-8602, Japan.
Takayuki
T
Suzuki
Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama Aoba-ku, Sendai 980-8578, Japan; Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Aobayama Aoba-ku, Sendai 980-8578, Japan.
Daisuke
D
Saito
Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama Aoba-ku, Sendai 980-8578, Japan.
Hitoshi
H
Yokoyama
Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama Aoba-ku, Sendai 980-8578, Japan. Electronic address: tam@m.tohoku.ac.jp.
Koji
K
Tamura
D000015:Abnormalities, Multiple / Q000209:etiology; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002642:Chick Embryo; D002645:Chickens; D004374:Ductus Arteriosus, Patent / Q000209:etiology; D005121:Extremities / Q000196:embryology*; D005145:Face / Q000002:abnormalities; D005346:Fibroblast Growth Factors / Q000502:physiology; D005385:Fingers / Q000002:abnormalities; D053823:Hedgehog Proteins / Q000502:physiology; D006801:Humans; D018878:Limb Buds / Q000196:embryology / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D015398:Signal Transduction; D050656:Transcription Factor AP-2 / Q000502:physiology*; D014158:Transcription, Genetic
D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D050656:Transcription Factor AP-2; D005346:Fibroblast Growth Factors
AP-2β; Char syndrome; Limb development; Transcriptional regulation