Hox patterning of the vertebrate axial skeleton

The axial skeleton in all vertebrates is composed of similar components that extend from anterior to posterior along the body axis: the occipital skull bones and cervical, thoracic, lumbar, sacral, and caudal vertebrae. Despite significant changes in the number and size of these elements during evolution, the basic character of these anatomical elements, as well as the order in which they appear in vertebrate skeletons, have remained remarkably similar. Through extensive expression analyses, classic morphological perturbation experiments in chicken and targeted loss-of-function analyses in mice, Hox genes have proven to be critical regulators in the establishment of axial skeleton morphology. The convergence of these studies to date allows an emerging understanding of Hox gene function in patterning the vertebrate axial skeleton. This review summarizes genetic and embryologic findings regarding the role of Hox genes in establishing axial morphology and how these combined results impact our current understanding of the vertebrate Hox code. Developmental Dynamics 236:2454–2463, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56149/1/21286_ftp.pd

The combined effect of two mutations that alter serially homologous color pattern elements on the fore and hindwings of a butterfly

<p>Abstract</p> <p>Background</p> <p>The ability for serially homologous structures to acquire a separate identity has been primarily investigated for structures dependent on Hox gene input but is still incompletely understood in other systems. The fore and hindwings of butterflies are serially homologous structures as are the serially homologous eyespots that can decorate each of these wings. Eyespots can vary in number between fore and hindwings of the same individual and mutations of large effect can control the total number of eyespots that each of the wings displays. Here we investigate the genetics of a new spontaneous color pattern mutation, <it>Missing</it>, that alters eyespot number in the nymphalid butterfly, <it>Bicyclus anynana</it>. We further test the interaction of <it>Missing </it>with a previously described mutation, <it>Spotty</it>, describe the developmental stage affected by <it>Missing</it>, and test whether <it>Missing </it>is a mutant variant of the gene <it>Distal-less </it>via a linkage association study.</p> <p>Results</p> <p><it>Missing </it>removes or greatly reduces the size of two of the hindwing eyespots from the row of seven eyespots, with no detectable effect on the rest of the wing pattern. Offspring carrying a single <it>Missing </it>allele display intermediate sized eyespots at these positions. <it>Spotty </it>has the opposite effect of <it>Missing</it>, i.e., it introduces two extra eyespots in homologous wing positions to those affected by <it>Missing</it>, but on the forewing. When <it>Missing </it>is combined with <it>Spotty </it>the size of the two forewing eyespots decreases but the size of the hindwing spots stays the same, suggesting that these two mutations have a combined effect on the forewing such that <it>Missing </it>reduces eyespot size when in the presence of a <it>Spotty </it>mutant allele, but that <it>Spotty </it>has no effect on the hindwing. <it>Missing </it>prevents the complete differentiation of two of the eyespot foci on the hindwing. We found no evidence for any linkage between the <it>Distal-less </it>and <it>Missing </it>genes.</p> <p>Conclusion</p> <p>The spontaneous mutation <it>Missing </it>controls the differentiation of the signaling centers of a subset of the serial homologous eyespots present on both the fore and the hindwing in a dose-dependent fashion. The effect of <it>Missing </it>on the forewing, however, is only observed when the mutation <it>Spotty </it>introduces additional eyespots on this wing. <it>Spotty</it>, on the other hand, controls the differentiation of eyespot centers only on the forewing. <it>Spotty</it>, unlike <it>Missing</it>, may be under Ubx gene regulation, since it affects a subset of eyespots on only one of the serially homologous wings.</p

Mesenchymal patterning by Hoxa2 requires blocking Fgf-dependent activation of Ptx1

Hox genes are known key regulators of embryonic segmental identity, but little is known about the mechanisms of their action. To address this issue, we have analyzed how Hoxa2 specifies segmental identity in the second branchial arch. Using a subtraction approach, we found that Ptx1 was upregulated in the second arch mesenchyme of Hoxa2 mutants. This upregulation has functional significance because, in Hoxa2-/-; Ptx1-/- embryos, the Hoxa2-/- phenotype is partially reversed. Hoxa2 interferes with the Ptx1 activating process, which is dependent on Fgf signals from the epithelium. Consistently, Lhx6, another target of Fgf8 signaling, is also upregulated in the Hoxa2-/- second arch mesenchyme. Our findings have important implications for the understanding of developmental processes in the branchial area and suggest a novel mechanism for mesenchymal patterning by Hox genes that acts to define the competence of mesenchymal cells to respond to skeletogenic signals

Cdx and Hox genes differentially regulate posterior axial growth in mammalian embryos.

Hox and Cdx transcription factors regulate embryonic positional identities. Cdx mutant mice display posterior body truncations of the axial skeleton, neuraxis, and caudal urorectal structures. We show that trunk Hox genes stimulate axial extension, as they can largely rescue these Cdx mutant phenotypes. Conversely, posterior (paralog group 13) Hox genes can prematurely arrest posterior axial growth when precociously expressed. Our data suggest that the transition from trunk to tail Hox gene expression successively regulates the construction and termination of axial structures in the mouse embryo. Thus, Hox genes seem to differentially orchestrate posterior expansion of embryonic tissues during axial morphogenesis as an integral part of their function in specifying head-to-tail identity. In addition, we present evidence that Cdx and Hox transcription factors exert these effects by controlling Wnt signaling. Concomitant regulation of Cyp26a1 expression, restraining retinoic acid signaling away from the posterior growth zone, may likewise play a role in timing the trunk-tail transition.

Biochemistry and molecular biology in Portugal: an overview of past and current contributions

Portugal, represented by the Portuguese Biochemical Society, has been a long-standing member of the IUBMB and a founding member of FEBS.Sociedade Portuguesa de Bioquímic