title: Anterior shift in gene expression precedes anteriormost digit formation in amniote limbs.
abstract: In tetrapod limbs, an anteriormost digit has common traits of small, short and less-phalange morphology. In this study, we focused on three genes, Mkp3, Sef and Tsukushi (TSK), which have anterior-specific or anterior-prominent expression patterns in the developing limb bud at the autopod-forming stage. The anterior expression is not fixed in the period of limb development, but the expression domains of Mkp3, Sef and TSK change considerably from the distal domain to the anterior domain. This change in expression domains, anterior shift, of these genes involves maintenance of gene expression in the anterior side and downregulation in the posterior side. Manipulated overdose of fibroblast growth factor (FGF) in the presumptive digit 2 region of chick forelimb bud results in elongation of cartilage elements of digit 2, suggesting that attenuated FGF signaling, which Mkp3, Sef, and TSK negatively regulate, provides digit 2-specific traits of morphology. The anterior expression of Mkp3 and Sef but not TSK is conserved also in limb buds of the mouse and gecko, and the anterior shift of these genes, accumulation of their transcripts in the anterior side and appropriate regulation of strength of FGF signaling may control species-specific morphology of the anteriormost digit.
authors.affiliation: Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Asaka
authors.initials: A
authors.lastname: Uejima
authors.forename: Takanori
authors.initials: T
authors.lastname: Amano
authors.forename: Naoki
authors.initials: N
authors.lastname: Nomura
authors.forename: Miyuki
authors.initials: M
authors.lastname: Noro
authors.forename: Taiji
authors.initials: T
authors.lastname: Yasue
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shiroishi
authors.forename: Kunimasa
authors.initials: K
authors.lastname: Ohta
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Koji
authors.initials: K
authors.lastname: Tamura
mesh_terms: D000818:Animals; D002642:Chick Embryo; D054642:Dual Specificity Phosphatase 6 / Q000235:genetics*; D005121:Extremities / Q000033:anatomy & histology* / Q000196:embryology*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008648:Mesoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C469338:Sef protein, mouse; D005346:Fibroblast Growth Factors; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase; D054642:Dual Specificity Phosphatase 6; C517036:Dusp6 protein, mouse