Novel regulation of the homeotic gene Scr associated with a crustacean leg-to-maxilliped appendage transformation.
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Homeotic genes are known to be involved in patterning morphological structures along the antero-posterior axis of insects and vertebrates. Because of their important roles in development, changes in the function and expression patterns of homeotic genes may have played a major role in the evolution of different body plans. For example, it has been proposed that during the evolution of several crustacean lineages, changes in the expression patterns of the homeotic genes Ultrabithorax and abdominal-A have played a role in transformation of the anterior thoracic appendages into mouthparts termed maxillipeds. This homeotic-like transformation is recapitulated at the late stages of the direct embryonic development of the crustacean Porcellio scaber (Oniscidea, Isopoda). Interestingly, this morphological change is associated with apparent novelties both in the transcriptional and post-transcriptional regulation of the Porcellio scaber ortholog of the Drosophila homeotic gene, Sex combs reduced (Scr). Specifically, we find that Scr mRNA is present in the second maxillary segment and the first pair of thoracic legs (T1) in early embryos, whereas protein accumulates only in the second maxillae. In later stages, however, high levels of SCR appear in the T1 legs, which correlates temporally with the transformation of these appendages into maxillipeds. Our observations provide further insight into the process of the homeotic leg-to-maxilliped transformation in the evolution of crustaceans and suggest a novel regulatory mechanism for this process in this group of arthropods. (+info)
The homeobox gene Pitx2: mediator of asymmetric left-right signaling in vertebrate heart and gut looping.
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Left-right asymmetry in vertebrates is controlled by activities emanating from the left lateral plate. How these signals get transmitted to the forming organs is not known. A candidate mediator in mouse, frog and zebrafish embryos is the homeobox gene Pitx2. It is asymmetrically expressed in the left lateral plate mesoderm, tubular heart and early gut tube. Localized Pitx2 expression continues when these organs undergo asymmetric looping morphogenesis. Ectopic expression of Xnr1 in the right lateral plate induces Pitx2 transcription in Xenopus. Misexpression of Pitx2 affects situs and morphology of organs. These experiments suggest a role for Pitx2 in promoting looping of the linear heart and gut. (+info)
The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development.
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Csx/Nkx2.5 is a vertebrate homeobox gene with a sequence homology to the Drosophila tinman, which is required for the dorsal mesoderm specification. Recently, heterozygous mutations of this gene were found to cause human congenital heart disease (Schott, J.-J., Benson, D. W., Basson, C. T., Pease, W., Silberbach, G. M., Moak, J. P., Maron, B. J., Seidman, C. E. and Seidman, J. G. (1998) Science 281, 108-111). To investigate the functions of Csx/Nkx2.5 in cardiac and extracardiac development in the vertebrate, we have generated and analyzed mutant mice completely null for Csx/Nkx2.5. Homozygous null embryos showed arrest of cardiac development after looping and poor development of blood vessels. Moreover, there were severe defects in vascular formation and hematopoiesis in the mutant yolk sac. Interestingly, TUNEL staining and PCNA staining showed neither enhanced apoptosis nor reduced cell proliferation in the mutant myocardium. In situ hybridization studies demonstrated that, among 20 candidate genes examined, expression of ANF, BNP, MLC2V, N-myc, MEF2C, HAND1 and Msx2 was disturbed in the mutant heart. Moreover, in the heart of adult chimeric mice generated from Csx/Nkx2.5 null ES cells, there were almost no ES cell-derived cardiac myocytes, while there were substantial contributions of Csx /Nkx2.5-deficient cells in other organs. Whole-mount &bgr;-gal staining of chimeric embryos showed that more than 20% contribution of Csx/Nkx2. 5-deficient cells in the heart arrested cardiac development. These results indicate that (1) the complete null mutation of Csx/Nkx2.5 did not abolish initial heart looping, (2) there was no enhanced apoptosis or defective cell cycle entry in Csx/Nkx2.5 null cardiac myocytes, (3) Csx/Nkx2.5 regulates expression of several essential transcription factors in the developing heart, (4) Csx/Nkx2.5 is required for later differentiation of cardiac myocytes, (5) Csx/Nkx2. 5 null cells exert dominant interfering effects on cardiac development, and (6) there were severe defects in yolk sac angiogenesis and hematopoiesis in the Csx/Nkx2.5 null embryos. (+info)
Insect evolution: Redesigning the fruitfly.
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Homeotic mutations in Drosophila can result in dramatic phenotypes that suggest the possibility for rapid morphological evolution, but dissection of the genetic pathway downstream of Ultrabithorax is beginning to reveal how wing morphology may have evolved by more gradual transformations. (+info)
Ultrabithorax function in butterfly wings and the evolution of insect wing patterns.
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BACKGROUND: . The morphological and functional evolution of appendages has played a critical role in animal evolution, but the developmental genetic mechanisms underlying appendage diversity are not understood. Given that homologous appendage development is controlled by the same Hox gene in different organisms, and that Hox genes are transcription factors, diversity may evolve from changes in the regulation of Hox target genes. Two impediments to understanding the role of Hox genes in morphological evolution have been the limited number of organisms in which Hox gene function can be studied and the paucity of known Hox-regulated target genes. We have therefore analyzed a butterfly homeotic mutant 'Hindsight', in which portions of the ventral hindwing pattern are transformed to ventral forewing identity, and we have compared the regulation of target genes by the Ultrabithorax (Ubx) gene product in Lepidopteran and Dipteran hindwings. RESULTS: . We show that Ubx gene expression is lost from patches of cells in developing Hindsight hindwings, correlating with changes in wing pigmentation, color pattern elements, and scale morphology. We use this mutant to study how regulation of target genes by Ubx protein differs between species. We find that several Ubx-regulated genes in the Drosophila haltere are not repressed by Ubx in butterfly hindwings, but that Distal-less (Dll) expression is regulated by Ubx in a unique manner in butterflies. CONCLUSIONS: . The morphological diversification of insect hindwings has involved the acquisition of different sets of target genes by Ubx in different lineages. Changes in Hox-regulated target gene sets are, in general, likely to underlie the morphological divergence of homologous structures between animals. (+info)
Loss-of-function mutations in the rice homeobox gene OSH15 affect the architecture of internodes resulting in dwarf plants.
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The rice homeobox gene OSH15 (Oryza sativa homeobox) is a member of the knotted1-type homeobox gene family. We report here on the identification and characterization of a loss-of-function mutation in OSH15 from a library of retrotransposon-tagged lines of rice. Based on the phenotype and map position, we have identified three independent deletion alleles of the locus among conventional morphological mutants. All of these recessive mutations, which are considered to be null alleles, exhibit defects in internode elongation. Introduction of a 14 kbp genomic DNA fragment that includes all exons, introns and 5'- and 3'- flanking sequences of OSH15 complemented the defects in internode elongation, confirming that they were caused by the loss-of-function of OSH15. Internodes of the mutants had abnormal-shaped epidermal and hypodermal cells and showed an unusual arrangement of small vascular bundles. These mutations demonstrate a role for OSH15 in the development of rice internodes. This is the first evidence that the knotted1-type homeobox genes have roles other than shoot apical meristem formation and/or maintenance in plant development. (+info)
Establishment of an inducible expression system of chimeric MLL-LTG9 protein and inhibition of Hox a7, Hox b7 and Hox c9 expression by MLL-LTG9 in 32Dcl3 cells.
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The MLL (HRX/ALL-1 gene is frequently disrupted in infantile leukemias and therapy-related leukemias and fused to various translocation partner genes. We previously showed that chimeric MLL proteins localize in the nuclei in a fashion similar to that of MLL protein even if the partner gene encodes a cytoplasmic protein and indicated the importance of the N-terminal portion of MLL common to various MLL translocations. This time we established an inducible expression system for chimeric MLL-LTG9 and truncated N-terminal MLL proteins (MLL-Zf(-)) in 32Dcl3 cells. By utilizing this system, we were able to show inhibition of Hox a7, Hox b7 and Hox c9 genes' expression by induced MLL-LTG9 and MLL-Zf(-). Up-regulation of Hox a7, Hox b7 and Hox c9 was observed when 32Dcl3 cells were cultured with granulocyte colony stimulating factor (G-CSF) in place of interleukin 3 and induction of MLL-LTG9 and MLL-Zf(-) was shown to suppress this upregulation. At the same time, expression of two mammalian Polycomb group genes, M33 and mel-18, which both reportedly affect Hox genes' expression, was not inhibited by MLL-LTG9 and MLL-Zf(-) induction. These results indicate that MLL has an important effect on the expression of at least some Hox genes in hematopoietic cells and suggest that inhibition of the proper expression of Hox genes by chimeric MLL proteins may dysregulate hematopoietic cell differentiation and proliferation, which then can lead to leukemogenesis. (+info)
The Caenorhabditis elegans gene ham-2 links Hox patterning to migration of the HSN motor neuron.
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The Caenorhabditis elegans HSN motor neurons permit genetic analysis of neuronal development at single-cell resolution. The egl-5 Hox gene, which patterns the posterior of the embryo, is required for both early (embryonic) and late (larval) development of the HSN. Here we show that ham-2 encodes a zinc finger protein that acts downstream of egl-5 to direct HSN cell migration, an early differentiation event. We also demonstrate that the EGL-43 zinc finger protein, also required for HSN migration, is expressed in the HSN specifically during its migration. In an egl-5 mutant background, the HSN still expresses EGL-43, but expression is no longer down-regulated at the end of the cell's migration. Finally, we find a new role in early HSN differentiation for UNC-86, a POU homeodomain transcription factor shown previously to act downstream of egl-5 in the regulation of late HSN differentiation. In an unc-86; ham-2 double mutant the HSNs are defective in EGL-43 down-regulation, an egl-5-like phenotype that is absent in either single mutant. Thus, in the HSN, a Hox gene, egl-5, regulates cell fate by activating the transcription of genes encoding the transcription factors HAM-2 and UNC-86 that in turn individually control some differentiation events and combinatorially affect others. (+info)