Axial Identity Research Articles

Transformations in null mutants of hox genes: Do they represent intercalary regenerates?

In the minds of many, Hox gene null mutant phenotypes have confirmed the direct role that these genes play in specifying the pattern of vertebrate embryos. The genes are envisaged as defining discrete spatial domains and, subsequently, conferring specific segmental identities on cells undergoing differentiation along the antero-posterior axis. However, several aspects of the observed mutant phenotypes are inconsistent with this view. These include: the appearance of other, unexpected transformations along the dorsal axis; the occurrence of mirror-image duplications; and the development of anomalies outside the established domains of normal Hox gene expression. In this paper, Hox gene disruptions are shown to elicit regeneration-like responses in tissues confronted with discontinuities in axial identity. The polarities and orientations of transformed segments which emerge as a consequence of this response obey the rules of distal transformation and intercalary regeneration. In addition, the incidence of periodic anomalies suggests that the initial steps of Hox-mediated patterning occurs in Hensen's node. As gastrulation proceeds, mesoderm cell cycle kinetics impose constraints upon subsequent cellular differentiation. This results in the delayed manifestation of transformations along the antero-posterior axis. Finally, a paradigm is sketched in which temporal, rather than spatial axial determinants direct differentiation. Specific, testable predictions are made about the role of Hox genes in the establishment of segmental identity.

The thyroid transcription factor-1 gene is a candidate target for regulation by Hox proteins.

Vertebrate Hox homeobox genes are transcription factors which regulate antero-posterior axial identity in embryogenesis, presumably through activation and/or repression of downstream target genes. Some of these targets were reported to code for molecules involved in cell-cell interactions, whereas no relationship has yet been demonstrated between Hox genes and other transcription factors involved in determining and/or maintaining tissue specificity. The thyroid transcription factor-1 (TTF-1) is a homeodomain-containing protein required for expression of thyroid-specific genes. A 862 bp 5' genomic fragment of the rat TTF-1 gene, conferring thyroid-specific expression to a reporter gene, was sufficient to mediate transactivation by the human HOXB3 gene in co-transfection assay in both NIH3T3 or HeLa cells. HOXB3 is expressed in early mammalian embryogenesis in the anterior neuroectoderm, branchial arches and their derivatives, including the area of the thyroid primordia and thyroid gland. Transcription of the TTF-1 promoter is induced only by HOXB3, while its paralogous gene HOXD3 or other Hox genes expressed more posteriorly (HOXA4, HOXD4, HOXC5, HOXC6, HOXC8 and Hoxd-8) have no effect. Transactivation by HOXB3 is mediated by two binding sites containing an ATTA core located at -100 and +30 from the transcription start site. DNase I footprinting experiments show that the two sites bind HOXB3 protein synthesized in both Escherichia coli and eukaryotic cells, as well as nuclear factor(s) present in protein extracts obtained from mouse embryonic tissues which express group 3 Hox genes and TTF-1. Some of the DNA-protein complexes formed by the embryonic extracts are indistinguishable from those generated by HOXB3.(ABSTRACT TRUNCATED AT 250 WORDS)

CHIRAL PERTURBATION THEORY AT THE QUARK LEVEL AND NEW NONPERTURBATIVE FORMULAE FOR THE PION DECAY CONSTANT IN QCD

Introducing the most general expression for the corresponding axial-vector vertex, the flavor nonsinglet, chiral axial-vector Ward-Takahashi (WT) identity is investigated in the framework of dynamical chiral symmetry breaking (DCSB). A chiral perturbation theory at the quark level (CHPTq) is proposed in terms of a Taylor series expansions in powers of the external momenta q (momentum of a massless pion) for the direct solution of the above identity at small momentum transfer q (momentum of a massless pion). Correct treatment of initial dynamical singularities at q=0 within the CHPTq approach in accordance with the Ball and Chiu procedure makes it possible to decompose the axial-vector vertex into pole and regular parts in a self-consistent way. The Bethe-Salpeter (BS) bound-state amplitude of a massless pion restored from the identity is shown to coincide with the residue at pole q2=0, which is proportional to the pion decay constant. We find exact solution for the regular piece of the corresponding vertex at zero momentum transfer in terms of the quark propagator dynamical variables alone. This solution automatically satisfies asymptotic freedom (it approaches the point-like vertex at infinity). Applying the proposed CHPTq approach to the matrix element of the axial-vector current determining the pion decay constant, we find “exact” (within the BS bound-state amplitude, restored fom the axial WT identity), nonperturbative expression for the pion decay constant in the current algebra (CA) representation. We show explicitly that the well-known formula of Pagels-Stokar-Cornwall for the pion decay constant is a particular case of the CHPTq approach. We find also new, nonperturbative formulae for the pion decay constant in the Jackiw-Johnson (JJ) representation as well. They now have full physical sense within the CHPTq approach. Renormalization of these expressions as well as their application in technicolor theories with slowly running couplings are briefly discussed. We also propose to distinguish between the scales of DCSB at the quark and hadronic levels (the scale of effective field theory) as well as advocate a simple relation between them based on naive counting arguments.

Control of morphogenesis and differentiation by HOM/Hox genes

HOM/Hox genes are master regulatory switches that specify axial identity and control the growth and differentiation of groups of cells related by position. HOM/Hox genes function combinatorially and hierarchically to specify cell fate. Some of the genes they regulate and that mediate specific identity functions have been identified. Research in Drosophila has shown that HOM genes are continuously required during development for correct axial identity.

Specification of axial identity in the mouse: role of the Hoxa-5 (Hox1.3) gene.

Numerous lines of study have suggested that the Hox genes, encoding putative transcription factors, are key genes in the establishment of the body plan of the mammalian embryo. To examine the role of Hoxa-5 (Hox1.3) gene during development, we have used targeted mutagenesis in embryonic stem cells to produce a strain of mice carrying a disrupted Hoxa-5 allele. The viability of homozygous mutant mice is markedly reduced, with 50% of the mutant animals dying at birth or shortly thereafter. Analysis of the skeleton of Hoxa-5 mutants reveals a number of homeotic transformations restricted to the cervical and thoracic regions. Of these, one of the most frequent morphological abnormalities is the posterior transformation of the seventh cervical vertebra into the likeness of a thoracic vertebra complete with a pair of ribs. These results demonstrate that the Hoxa-5 gene has an important role in the establishment of the skeleton during development and contributes to the process whereby the axial structures are determined.

Physical properties of the pion in the covariant Bethe-Salpeter formalism.

Some problems concerned with normalization of wave functions, which are obtained from the general method for the Lorentz-covariant Bethe-Salpeter equation of the Goldstone boson developed in our previous work, are discussed in connection with the axial Ward-Takahashi identity. Physical properties of the pion, including the ${\ensuremath{\pi}}^{0}\ensuremath{\rightarrow}\ensuremath{\gamma}\ensuremath{\gamma}$ amplitude, are calculated in QCD-motivated models with the general method. Both the chiral limit and the effect of explicit chiral-symmetry breaking by the bare quark mass are considered. A quite good agreement with experimental data is obtained with these models.