Homeobox genes in vertebrate evolution.

A wide range of anatomical features are shared by all vertebrates, but absent in our closest invertebrate relatives. The origin of vertebrate embryogenesis must have involved the evolution of new regulatory pathways to control the development of new features, but how did this occur? Mutations affecting regulatory genes, including those containing homeobox sequences, may have been important: for example, perhaps gene duplications allowed recruitment of genes to new roles. Here I ask whether comparative data on the genomic organization and expression patterns of homeobox genes support this hypothesis. I propose a model in which duplications of particular homeobox genes, followed by the acquisition of gene-specific secondary expression domains, allowed the evolution of the neural crest, extensive organogenesis and craniofacial morphogenesis. Specific details of the model are amenable to testing by extension of this comparative approach to molecular embryology.     

HOX Pro: a specialized database for clusters and networks of homeobox genes

It is now clear that the homeobox motif is well conserved across metazoan phyla. It has been established experimentally that a subset of genes containing this motif plays key roles in the orchestration of gene expression during development. Auto- and cross-regulatory functional interactions join homeobox genes into genetic networks. We have developed a specialized database HOX-Pro in order to arrange all available data on structure, function, phylogeny and evolution of Hox genes, Hox clusters and Hox networks. Its primary location is http://www.iephb.nw.ru/hoxpro. The database is also mirrored at http://www.mssm.edu/molbio/hoxpro. The HOX-Pro database is aimed at: (i) analysis and classification of regulatory and coding regions in diverse homeobox and related genes; (ii) comparative analysis of organization of 'Hox-based' genetic networks in the sea urchin Strongylocentrotus purpuratus, the fruit fly Drosophila melanogaster and the mouse Mus musculus; and (iii) analysis of phylogeny and evolution of homeobox genes and clusters.     

植物同源异型枢基因的研究进展

植物同源异型枢基因是涉及到植物个体发育的一类重要转录因子编码基因.这类基因及其编码蛋白的结构具有明显的保守性,在植物中广泛存在,研究这类基因,对于揭示植物的发育机制具有重要意义.     

Molecular Genetics and the Ontogeny of Pigment Patterns in Mammals

The conclusion that animal development is guided by a hierarchical system of gene expression and interaction has gained considerable support from recent molecular genetic studies on fruit flies (Drosophila melanogaster) and mice (Mus musculus). They demonstrate that the patterns of organization revealed by terminal differentiation of cells is anticipated by a myriad of transient prepatterns that channel the developing embryo toward its genetically-programmed target. The numerous white spotting mutants in mice exhibit some of the most dramatic and variable patterns of cutaneous melanin pigmentation. Until recently, the mechanisms of action of white spotting genes and their relationship to the developmental genetic hierarchy remained unknown. It now appears that certain white spotting genes may encode growth factors essential for melanoblast development. Others may be related to homeobox genes that play a number of developmental roles, the primary one being the determination of regional organization along the anterior-posterior axis of the early embryo. The patterns of homeobox gene expression are consistent with several of the developmental models for white spotting in mice and other mammals. It is evident that white spotting genes are not solely concerned with the terminal differentiation of melanoblasts into melanocytes. They are heterogeneous with regard to action and level of expression within the developmental hierarchy.     

Expression of Dlx genes during the development of the murine dentition

The mammalian Dlx homeobox gene family has been shown to play multiple roles in tooth development, but a detailed comparison of the expression pattern of all members throughout tooth development has been lacking. We provide such an analysis for the six known murine Dlx genes. The expression patterns for these genes allow a refinement of previously proposed models for the role of Dlx genes in tooth type specification and raise the possibility of roles for subsets of these genes in tooth initiation, morphogenesis (enamel navel formation, enamel knot induction, cervical loop growth), and enamel formation. The relationship of Dlx gene expression to their genomic organization suggests coordinate regulation of linked genes at early stages but regulatory differences at later stages. Received: 19 July 1999 / Accepted: 3 December 1999     

Homeobox Genes in the Developing Mouse Brain

Abstract: Any list of past and recent findings on vertebrate brain prenatal development would have to include the fundamental roles of homeobox genes, the genes encoding the nuclear regulatory homeodomain proteins. The discovery of homeobox genes and their involvement as master regulatory elements in programing the development of an embryo into a complete adult organism has provided a key to our understanding of ontogenesis. Also, the correlation of mouse developmental mutants and their corresponding human syndromes with mutations in homeobox genes has provided further evidence for the fundamental role of homeobox genes during the vertebrate brain embryonic development. Here, we review the expression patterns and the phenotypes of gene mutations that implicate a large repertoire of mouse homeobox genes in the specification of neuronal functions during brain embryogenesis.     

HomeoDB: a database of homeobox gene diversity

The homeobox genes are a large and diverse group of genes, many of which play important roles in the embryonic development of animals. Comparative study of homeobox genes, both within and between species, requires an evolutionary-based classification. HomeoDB was designed and implemented as a manually curated database to collect and present homeobox genes in an evolutionarily structured way, allowing genes, gene families and gene classes to be compared between species more readily than was possible previously. In its first release, HomeoDB includes all homeobox genes from human, amphioxus (Branchiostoma floridae) and fruitfly (Drosophila melanogaster); additional species can be added. HomeoDB is freely accessible at (http://homeodb.cbi.pku.edu.cn).     

Integrating differentiation and cancer: the Nkx3.1 homeobox gene in prostate organogenesis and carcinogenesis

Abstract Several tissue-specific regulatory genes have been found to play essential roles in both organogenesis and carcinogenesis. In the prostate, the Nkx3.1 homeobox gene plays an important role in normal differentiation of the prostatic epithelium while its loss of function is an initiating event in prostate carcinogenesis in both mouse models and human patients. Thus, the Nkx3.1 homeobox gene provides a paradigm for understanding the relationship between normal differentiation and cancer, as well as studying the roles of homeobox genes in these processes. Here, we review recent findings concerning the roles of Nkx3.1 in development and discuss how its normal function is disrupted in processes of early prostate carcinogenesis.     

Classification and nomenclature of all human homeobox genes

Background

The homeobox genes are a large and diverse group of genes, many of which play important roles in the embryonic development of animals. Increasingly, homeobox genes are being compared between genomes in an attempt to understand the evolution of animal development. Despite their importance, the full diversity of human homeobox genes has not previously been described.

Results

We have identified all homeobox genes and pseudogenes in the euchromatic regions of the human genome, finding many unannotated, incorrectly annotated, unnamed, misnamed or misclassified genes and pseudogenes. We describe 300 human homeobox loci, which we divide into 235 probable functional genes and 65 probable pseudogenes. These totals include 3 genes with partial homeoboxes and 13 pseudogenes that lack homeoboxes but are clearly derived from homeobox genes. These figures exclude the repetitive DUX1 to DUX5 homeobox sequences of which we identified 35 probable pseudogenes, with many more expected in heterochromatic regions. Nomenclature is established for approximately 40 formerly unnamed loci, reflecting their evolutionary relationships to other loci in human and other species, and nomenclature revisions are proposed for around 30 other loci. We use a classification that recognizes 11 homeobox gene 'classes' subdivided into 102 homeobox gene 'families'.

Conclusion

We have conducted a comprehensive survey of homeobox genes and pseudogenes in the human genome, described many new loci, and revised the classification and nomenclature of homeobox genes. The classification scheme may be widely applicable to homeobox genes in other animal genomes and will facilitate comparative genomics of this important gene superclass.     

Despite expression in embryonic visceral mesoderm, H2.0 is not essential for Drosophila visceral muscle morphogenesis.

H2.0, a homeobox gene identified by homology to the Sex combs reduced homeobox of Drosophila, is expressed in all the cellular precursors of the visceral musculature. By analogy to the essential function of most other known homeobox genes in determining the fate of cells where they are expressed, we hypothesized that mutation of H2.0 would disrupt gut muscle development. In this paper, we show that a small deletion, which eliminates H2.0, has no detectable effect on normal gut morphogenesis, visceral muscle actin organization, or larval peristalsis.     

Isolation and characterization of a rice homebox gene, OSH15

In many eukaryotic organisms including plants, homeobox genes are thought to be master regulators that establish the cellular or regional identities and specify the fundamental body plan. We isolated and characterized a cDNA designated OSH15 (Oryza sativa homeobox 15) that encodes a KNOTTED-type homeodomain protein. Transgenic tobacco plants overexpressing the OSH15 cDNA showed a dramatically altered morphological phenotype caused by disturbance of specific aspects of tobacco development, thereby indicating the involvement of OSH15 in plant development. We analyzed the in situ mRNA localization of OSH15 through the whole plant life cycle, comparing the expression pattern with that of another rice homeobox gene, OSH1. In early embryogenesis, both genes were expressed as the same pattern at a region where the shoot apical meristem would develop later. In late embryogenesis, the expression pattern of the two genes became different. Whereas the expression of OSH1 continued within the shoot apical meristem, OSH15 expression within the shoot apical meristem ceased but became observable in a ring shaped pattern at the boundaries of some embryonic organs. This pattern of expression was similar to that observed around vegetative or reproductive shoots, or the floral meristem in mature plants. RNA in situ localization data suggest that OSH15 may play roles in the shoot organization during early embryogenesis and thereafter, OSH15 may be involved in morphogenetic events around the shoot apical meristem.     

Evolutionary and polymorphic organization of the knotted1 homeobox in cereals

 Homeobox genes are the master control genes harbouring the homeobox which is crucial for developmental associated functions. One homeobox gene, knotted1, which has a role in leaf development, is conserved in plants and might have arisen from a single ancestral gene. Using PCR, we identified multiple kn1 homeoboxes in diverse cereals and showed a cereal/ species-specific organization correlating them to evolutionary changes. We postulate the insertion of a large intron preceded by duplication of the kn1 homeobox in the lineage leading to rice. Received: 17 October 1997 / Accepted: 9 December 1997     

Extensive chordate and annelid macrosynteny reveals ancestral homeobox gene organization

Genes with the homeobox motif are crucial in developmental biology and widely implicated in the evolution of development. The Antennapedia (ANTP)-class is one of the two major classes of animal homeobox genes, and includes the Hox genes, renowned for their role in patterning the anterior-posterior axis of animals. The origin and evolution of the ANTP-class genes are a matter of some debate. A principal guiding hypothesis has been the existence of an ancient gene Mega-cluster deep in animal ancestry. This hypothesis was largely established from linkage data from chordates, and the Mega-cluster hypothesis remains to be seriously tested in protostomes. We have thus mapped ANTP-class homeobox genes to the chromosome level in a lophotrochozoan protostome. Our comparison of gene organization in Platynereis dumerilii and chordates indicates that the Mega-cluster, if it did exist, had already been broken up onto four chromosomes by the time of the protostome-deuterostome ancestor (PDA). These results not only elucidate an aspect of the genome organization of the PDA but also reveal high levels of macrosynteny between P. dumerilii and chordates. This implies a very low rate of interchromosomal genome rearrangement in the lineages leading to P. dumerilii and the chordate ancestor since the time of the PDA.