Medaka unextended-fin mutants suggest a role for Hoxb8a in cell migration and osteoblast differentiation during appendage formation

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2006.02.017 Byline: Sae Sakaguchi (a), Yuki Nakatani (a), Naofumi Takamatsu (b), Hiroshi Hori (b), Atsushi Kawakami (a), Keiji Inohaya (a), Akira Kudo (a) Keywords: Medaka; Oryzias latipes; hoxb8a; fin; Cell migration; Osteoblast; wnt5a Abstract: Hoxb8 has been suggestively implicated in the formation of the zone of polarizing activity (ZPA) in the limb bud. However, as hoxb8.sup.-/- mice did not show any defects in their limb development, the role of Hoxb8 during limb development has not been fully elucidated. Here, we report the identification of the medaka hoxb8a mutant, unextended-fin (ufi), in which all the fin tissues were malformed. Since the abnormal phenotype was observed in the caudal fin, the ufi phenotype suggests that the medaka Hoxb8a has a fundamental role in the formation of appendages protruding from the trunk. Our analyses revealed that the expression of wnt5a, a regulator of cell migration that signals through the non-canonical Wnt/Ca.sup.2+ pathway, was down-regulated in the ufi fin-folds. In fact, we found that the proximal-distal cell migration was impaired in ufi mutants and that the defect could be reversed by the injection of a Wnt5a protein. Moreover, we show herein that the numbers of proliferating cells and osteoblastic cells were increased in the ufi mutants. According to these results, we propose that the medaka Hoxb8a protein functions in the outgrowth of appendages through the regulation of cell migration and osteoblast differentiation. Author Affiliation: (a) Department of Biological Information, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan (b) Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan Article History: Received 17 January 2006; Revised 8 February 2006; Accepted 13 February 2006