Hox gene expression in teleost fins and the origin of vertebrate digits

HOX genes are essential for growth and patterning of the tetrapod limb skeleton1–5. Mice mutant for the Hoxd-13gene have an important delay in morphogenesis owing to reduced proliferation2. Based on the appearance of atavisms in such mice, we suggested that modifications of Hox gene regulation may have been a source of morphological variation during the evolution of tetrapod limbs2,6. Pectoral and pelvic fins are homologous to fore- and hind-limbs, respectively. To compare the relative importance of Hox genes during fin versus limb morphogenesis, we cloned zebrafish (Danio rerio) HoxD and HoxA complex genes and analysed their expression during fin development. The results suggest a scheme for the fin–limb transition in which the distal autopods (digits) are neomorphic structures produced by unequal proliferation of the posterior part of an ancestral appendix.

[1]  Nils Holmgren AN EMBRYOLOGICAL ANALYSIS OF THE MAMMALIAN CARPUS AND ITS BEARING UPON THE QUESTION OF THE ORIGIN OF THE TETRAPOD LIMB , 1952 .

[2]  D. SUMMERBELL,et al.  Positional Information in Chick Limb Morphogenesis , 1973, Nature.

[3]  J. Géraudie The Fine Structure of the Early Pelvic Fin Bud of the Trouts Salmo gairdneri and S. trutta fario , 1978 .

[4]  J. Hinchliffe The development of the vertebrate limb , 1980 .

[5]  P. Alberch,et al.  A morphogenetic approach to the origin and basic organization of the tetrapod limb , 1986 .

[6]  G. Streisinger,et al.  Segregation analyses and gene-centromere distances in zebrafish. , 1986, Genetics.

[7]  Denis Duboule,et al.  Coordinate expression of the murine Hox-5 complex homoeobox-containing genes during limb pattern formation , 1989, Nature.

[8]  A. Kuroiwa,et al.  Homeobox gene expression correlated with the bifurcation process of limb cartilage development , 1991, Nature.

[9]  P. Thorogood The Development of the Teleost Fin and Implications for Our Understanding of Tetrapod Limb Evolution , 1991 .

[10]  Clifford J. Tabin,et al.  Retinoids, homeoboxes, and growth factors: Toward molecular models for limb development , 1991, Cell.

[11]  J. Hinchliffe,et al.  Developmental Patterning of the Vertebrate Limb , 1991, NATO ASI Series.

[12]  D. Duboule,et al.  Homeobox genes and pattern formation in the vertebrate limb. , 1992, Developmental biology.

[13]  S. Potter,et al.  Homeotic transformations and limb defects in Hox A11 mutant mice. , 1993, Genes & development.

[14]  Denis Duboule,et al.  Disruption of the Hoxd-13 gene induces localized heterochrony leading to mice with neotenic limbs , 1993, Cell.

[15]  P. Ingham,et al.  A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos , 1993, Cell.

[16]  P. Gruss,et al.  The establishment of murine Hox-1 expression domains during patterning of the limb. , 1993, Developmental biology.

[17]  C. Tabin,et al.  Sonic hedgehog mediates the polarizing activity of the ZPA , 1993, Cell.

[18]  T. Potthoff,et al.  Osteological development of the snook, Centropomus uncedimalis (Teleostei, Centropomidae) , 1993 .

[19]  M. Capecchi,et al.  Axial homeosis and appendicular skeleton defects in mice with a targeted disruption of hoxd-11. , 1994, Development.

[20]  P. Ahlberg,et al.  The origin and early diversification of tetrapods , 1994, Nature.

[21]  D. Duboule,et al.  How to make a limb? , 1994, Science.

[22]  C. Tickle,et al.  A positive feedback loop coordinates growth and patterning in the vertebrate limb , 1994, Nature.

[23]  C. Tabin,et al.  Sonic hedgehog and Fgf-4 act through a signaling cascade and feedback loop to integrate growth and patterning of the developing limb bud , 1994, Cell.

[24]  N. Shubin The Evolution of Paired Fins and the Origin of Tetrapod Limbs , 1995 .

[25]  P. Chambon,et al.  Axial skeleton homeosis and forelimb malformations in Hoxd-11 mutant mice. , 1995, Proceedings of the National Academy of Sciences of the United States of America.