DOCSLIB.ORG

Ultrabithorax Is Essential for Bacteriocyte Development

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Ultrabithorax Is Essential for Bacteriocyte Development Ultrabithorax is essential for bacteriocyte development Yu Matsuuraa,b,c, Yoshitomo Kikuchid, Toru Miurab, and Takema Fukatsua,c,1 aBioproduction Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8566, Japan; bGraduate School of Environmental Science, Hokkaido University, Sapporo 060-0810, Japan; cGraduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan; and dBioproduction Research Institute, National Institute of Advanced Industrial Science and Technology, Hokkaido Center, Sapporo 062-8517, Japan Edited by Nancy A. Moran, University of Texas at Austin, Austin, TX, and approved June 19, 2015 (received for review February 18, 2015) Symbiosis often entails the emergence of novel adaptive traits in transcription factors, in particular Ultrabithorax (Ubx), are involved organisms. Microbial symbionts are indispensable for diverse insects in the development of the host cells and organs specialized for via provisioning of essential nutrients, wherein novel host cells and harboring the symbiotic bacteria. organs for harboring the microbes, called bacteriocytes and bacter- iomes, have evolved repeatedly. Molecular and developmental mech- Results and Discussion anisms underpinning the emergence of novel symbiotic cells and Bacteriocyte Development During Embryogenesis of N. plebeius. We organs comprise an unsolved question in evolutionary developmental performed a detailed description of the embryogenesis of N. ple- biology. Here, we report that a conserved homeotic gene, Ultra- beius with special focus on the dynamics of the bacteriocyte- bithorax, plays a pivotal role in the bacteriocyte differentiation in a associated gammaproteobacterial symbiont “Candidatus Schneideria hemipteran insect Nysius plebeius. During embryonic development, nysicola” (18) (Figs. 1 and 2, Table S1,andMovie S1). The sym- six pairs of aggregated presumptive bacteriocytes appear on both biotic bacteria were found as an aggregate at the anterior pole of sides of six abdominal segments, incorporate the symbiotic bacteria newly laid eggs (Fig. 1 A and B). After blastoderm formation at the stage of germband retraction, and fuse into a pair of lateral (12–24 h after oviposition; Fig. 2A) and germband elongation bacteriomes at the stage of germband flip, where bacteriocyte-asso- (24–33 h; Fig. 2 B–D), the symbionts were wrapped within ab- ciated Ultrabithorax expression coincides with the symbiont infec- dominal segments of the germband (36–60 h; Figs. 1 I and J and 2 tion process. Suppression of Ultrabithorax expression by maternal E–G). After germband retraction (∼72 h; Fig. 2H), the symbionts RNA interference results in disappearance of the bacteriocytes and migrated from the abdominal population to presumptive bacter- EVOLUTION the symbiont localization therein, suggesting that Ultrabithorax is iocytes that appeared on both sides of abdominal segments A2–A7 involved in differentiation of the host cells for symbiosis. Suppression as six pairs of clusters (72–84 h; Figs. 1 K and L and 2 I and J). of other homeotic genes abdominal-A and Antennapedia disturbs Then, during the process of drastic embryonic flip called katatrepsis, integrity and positioning of the bacteriomes, affecting the configura- the six bacteriocyte clusters on each side fused into a coherent tion of the host organs for symbiosis. Our findings unveil the molec- bacteriome located at abdominal segments A2–A4 (84–96 h; ular and developmental mechanisms underlying the bacteriocyte Figs. 1 M and N, and 2 K–M and Q–R). After the symbiont in- differentiation, which may have evolved either via cooption of the fection, the bacteriocytes accumulated red pigment and became transcription factors for inducing the novel symbiotic cells, or via re- easily recognizable (∼84 h; Figs. 1 C and 2 R–T). The red pig- vival of the developmental pathway for the bacteriocytes that had mentation provided a visible marker useful for tracing the existedintheancestralhemipterans. bacteriocytes, although it is unclear whether the red pigment was derived from the symbiont or the host. bacteriocyte | homeotic gene | transcription factor | evolution | symbiosis Significance ymbiosis is the source of novel adaptive traits, thereby con- Stributing to organismal evolution and diversification (1, 2). A Among the most fundamental questions in developmental bi- variety of insects are obligatorily dependent on microbial sym- ology is how novel cell types have emerged in the metazoan bionts via provisioning of essential nutrients lacking in their diets evolution. Among the most challenging questions in evolu- (3, 4), wherein novel host cells and organs for harboring the mi- tionary biology is how sophisticated symbiotic associations crobes, called bacteriocytes and bacteriomes, have evolved repeat- have evolved through less intimate interorganismal in- edly in such insect groups as hemipterans (aphids, whiteflies, – teractions. These fundamental biological issues are crystalized mealybugs, leafhoppers, spittlebugs, etc.) (5 9), dipterans (tsetse in the evolution and development of insect’s bacteriocytes flies, bat flies, etc.) (10, 11), coleopterans (weevils, etc.) (12, 13), specialized for harboring symbiotic bacteria. Here, we report and many others (14). Despite a considerable body of embryo- that a conserved transcription factor Ultrabithorax is essential logical descriptions (14), molecular mechanisms underlying the for bacteriocyte development in an insect, thereby uncovering bacteriocyte differentiation have been a long-lasting enigma in a molecular mechanism underlying the emergence of the novel evolutionary developmental biology (15, 16). Although cellular host cells for symbiosis. Our finding highlights the importance and developmental aspects of the bacteriocyte formation have of developmental cooption of preexisting transcription factors Acyrthosiphon pisum been best documented for the pea aphid, and sheds new light on a long-lasting enigma in evolutionary Nysius plebeius (5, 15, 17), the seed bug and allied heteropteran developmental biology. bugs of the superfamily Lygaeoidea have recently emerged as a promising model system for investigating the development, evo- Author contributions: Y.M. and T.F. designed research; Y.M., Y.K., and T.M. performed lution, and origin of the bacteriocytes, on the grounds that research; Y.M. analyzed data; and Y.M. and T.F. wrote the paper. (i) heteropteran bugs are generally associated with gut symbiotic The authors declare no conflict of interest. bacteria without bacteriocytes; (ii) thus, the bacteriocytes in these This article is a PNAS Direct Submission. lygaeoid species are regarded as a novel trait whose evolution was Freely available online through the PNAS open access option. iii N. plebeius a relatively recent event (18, 19); and ( )in and allied Data deposition: The nucleotide sequences determined in this study have been deposited lygaeoid species, RNA interference (RNAi) works efficiently, in the DNA Data Bank of Japan database (accession nos. LC010622–LC010625). which enables functional analysis of genes involved in the bac- 1To whom correspondence should be addressed. Email: [email protected]. teriocyte formation (20, 21). Here we demonstrate that, by making This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. use of the emerging model insect N. plebeius, conserved homeobox 1073/pnas.1503371112/-/DCSupplemental. www.pnas.org/cgi/doi/10.1073/pnas.1503371112 PNAS Early Edition | 1of6 Downloaded by guest on September 30, 2021 Fig. 1. Symbiont localization and bacteriocyte differentiation during the development of N. plebeius.(A and B) Newly laid eggs. (C and D) Embryos 5 d after oviposition. (E and F) First-instar nymphs. (G and H) Adult insects. (I and J) Embryos ∼48 h after oviposition. (K and L) Embryos of 72–84 h. (M and N) Embryos of ∼96 h. (O and P) Embryos of ∼120 h. A, C, E, and G are light-microscopic images; I, K, M, and O are schematic illustrations of symbiont localization (red) in the embryos; and B, D, F, H, J, L, N,andP are fluorescence microscopic images in which blue and green signals show the host nuclei and the symbiotic bacteria, respectively. Arrowheads depict bacteriocytes, and arrows indicate aggregated symbionts within the embryos. A1, A2, and A3, first, second, and third abdominal segments, respectively; ob, ovarial bacteriocytes in adult female; T3, third thoracic segment. Bacteriocyte-Associated Expression of Ubx in Embryogenesis of abdominal segments A2–A7 after the germband retraction (Fig. 3 N. plebeius. The homeobox genes encode transcription factors B–D and Fig. S1D), which agreed with the locations of the pre- that assign segment identities and specify functional body parts sumptive bacteriocytes (Figs. 1 K and L and 2J). Meanwhile, abd-A in the development of insects and other animals (16, 22). In the was expressed broadly across the abdominal segments without embryogenesis of the pea aphid A. pisum, some homeobox gene specific association with the presumptive bacteriocytes (Fig. 3 E products—including an appendage-patterning transcription fac- and F and Fig. S1 H–J). tor Distal-less (Dll), homeotic proteins Ubx or Abdominal-A (Abd-A), and a segment polarity protein Engrailed (En)—were Disappearance of Bacteriocytes by Ubx Suppression. In heteropteran shown to localize to the bacteriocytes, although their functions in species including O. fasciatus, injection of double-stranded RNA the symbiotic cells have been
Load more

Recommended publications
  • Long Noncoding Rnas: Functional Surprises from the RNA World
    Downloaded from genesdev.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Long noncoding RNAs: functional surprises from the RNA world Jeremy E. Wilusz,1 Hongjae Sunwoo,2 and David L. Spector1,3 1Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA; 2Graduate Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, New York 11794 Most of the eukaryotic genome is transcribed, yielding complexity. In addition, there has been an explosion of a complex network of transcripts that includes tens of research addressing possible functional roles for the thousands of long noncoding RNAs with little or no other 98% of the human genome that does not encode protein-coding capacity. Although the vast majority of proteins. Rather unexpectedly, transcription is not lim- long noncoding RNAs have yet to be characterized thor- ited to protein-coding regions, but is instead pervasive oughly, many of these transcripts are unlikely to represent throughout the mammalian genome as demonstrated by transcriptional ‘‘noise’’ as a significant number have been large-scale cDNA cloning projects (Carninci et al. 2005; shown to exhibit cell type-specific expression, localiza- Katayama et al. 2005) and genomic tiling arrays (Bertone tion to subcellular compartments, and association with et al. 2004; Cheng et al. 2005; Birney et al. 2007; Kapranov human diseases. Here, we highlight recent efforts that et al. 2007a). In fact, >90% of the human genome is likely have identified a myriad of molecular functions for long to be transcribed (Birney et al. 2007), yielding a complex noncoding RNAs.
    [Show full text]
  • Perspectives
    Copyright 0 1994 by the Genetics Society of America Perspectives Anecdotal, Historical and Critical Commentaries on Genetics Edited by James F. Crow and William F. Dove A Century of Homeosis, A Decade of Homeoboxes William McGinnis Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114 NE hundred years ago, while the science of genet- ing mammals, and were proposed to encode DNA- 0 ics still existed only in the yellowing reprints of a binding homeodomainsbecause of a faint resemblance recently deceased Moravian abbot, WILLIAMBATESON to mating-type transcriptional regulatory proteins of (1894) coined the term homeosis to define a class of budding yeast and an even fainter resemblance to bac- biological variations in whichone elementof a segmen- terial helix-turn-helix transcriptional regulators. tally repeated array of organismal structures is trans- The initial stream of papers was a prelude to a flood formed toward the identity of another. After the redis- concerning homeobox genes and homeodomain pro- coveryof MENDEL’Sgenetic principles, BATESONand teins, a flood that has channeled into a steady river of others (reviewed in BATESON1909) realized that some homeo-publications, fed by many tributaries. A major examples of homeosis in floral organs and animal skel- reason for the continuing flow of studies is that many etons could be attributed to variation in genes. Soon groups, working on disparate lines of research, have thereafter, as the discipline of Drosophila genetics was found themselves swept up in the currents when they born and was evolving into a formidable intellectual found that their favorite protein contained one of the force enriching many biologicalsubjects, it gradually be- many subtypes of homeodomain.
    [Show full text]
  • REVIEW Cell and Molecular Biology of Notch
    459 REVIEW Cell and molecular biology of Notch Ulla-Maj Fiu´za and Alfonso Martinez Arias Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK (Correspondence should be addressed to U-M Fiu´za; Email: [email protected]) Abstract Notch signalling is a cell–cell communication process, which complexity which could account for the multitude of roles it has allows the establishment of patterns of gene expression and during development and in adult organisms. In this review, we differentiation, regulates binary cell fate choice and the will describe the multiple roles of Notch and how various factors maintenance of stem cell populations. So far, the data published can regulate Notch signalling. has elucidated the main players in the Notch signalling pathway. Journal of Endocrinology (2007) 194, 459–474 However, its regulatory mechanisms are exhibiting an increasing The structure of Notch and the Notch signalling which allowed the discovery of a core set of molecules involved pathway in Notch signalling and lead to the understanding of how they organize into a signalling pathway. The Notch genes encode members of a family of receptors that In mammals, there are four Notch genes and five genes mediate short-range signalling events. A prototypical Notch encoding ligands, three Delta-like and two Jagged (Fig. 1). In gene encodes a single transmembrane receptor composed in Drosophila, there is only one Notch-encoding gene, one Delta its extracellular region of a conserved array of up to 36 and one Jagged homologue (Serrate; Maine et al. 1995, epidermal growth factor (EGF)-like repeats, involved in Lissemore & Starmer 1999).
    [Show full text]
  • Epigenetics of Floral Homeotic Genes in Relation to Sexual Dimorphism in the 2 Dioecious Plant Mercurialis Annua
    bioRxiv preprint doi: https://doi.org/10.1101/481481; this version posted November 29, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Epigenetics of floral homeotic genes in relation to sexual dimorphism in the 2 dioecious plant Mercurialis annua 3 4 Janardan Khadka1, Narendra Singh Yadav1†, Micha Guy1, Gideon Grafi1* and Avi Golan- 5 Goldhirsh1* 6 1French Associates Institute for Agriculture and Biotechnology of Drylands, Jacob Blaustein 7 Institutes for Desert Research, Ben-Gurion University of the Negev, Midreshet Ben Gurion 8 84990, Israel. 9 †Present address: Department of Biological Sciences, University of Lethbridge, AB T1K 10 3M4, Canada. 11 * To whom correspondence should be addressed 12 13 14 Highlights 15 Sex determination in Mercurialis annua is not related to epigenetics of floral homeotic genes 16 but appears to be modulated by an unknown gender-specific regulator(s) that affects hormonal 17 homeostasis. 18 1 bioRxiv preprint doi: https://doi.org/10.1101/481481; this version posted November 29, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 19 Abstract 20 In plants, dioecy characterizes species carrying male and female flowers on separate plants 21 and occurs in about 6% of angiosperms. To date, the molecular mechanism(s) underlying 22 sexual dimorphism is essentially unknown. The ability of gender-reversal by hormone 23 application suggests that epigenetics might play an important role in sexual dimorphism.
    [Show full text]
  • Phosphorylation, Expression and Function of the Ultrabithorax Protein Family in Drosophila Melanogaster
    Development 112, 1077-1093 (1991) 1077 Printed in Great Britain © The Company of Biologists Limited 1991 Phosphorylation, expression and function of the Ultrabithorax protein family in Drosophila melanogaster ELIZABETH R. GAVIS* and DAVID S. HOGNESSt't Department of Biochemistry, Beckman Center, Stanford University School of Medicine, Stanford, California 94305 USA * Present address: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142 USA t Present address: Department of Developmental Biology, Beckman Center, Stanford University School of Medicine, Stanford, California, 94305 USA $ Author for correspondence Summary Alternative splicing of the Ultrabithorax homeotic gene parallel those for the respective mRNAs, and all transcript generates a family of five proteins (UBX isoforms are similarly phosphorylated throughout em- isoforms) that function as transcription factors. All bryogenesis. Analysis by cotransfection assays of the isoforms contain a homeodomain within a common 99 aa promoter activation and repression functions of mutant C-terminal region (C-constant region) which is joined to UBX proteins with various deletions in the N-constant a common 247 aa N-terminal (N-constant) region by region shows that repression is generally insensitive to different combinations of three small optional elements. deletion and, hence, presumably to phosphorylation. By Unlike the UBX proteins expressed in E. coli, UBX contrast, the activation function is differentially sensitive isoforms expressed in D. melanogaster cells are phos- to the different deletions in a manner indicating the phorylated on serine and threonine residues, located absence of a discrete activating domain and instead, the primarily within a 53 aa region near the middle of the presence of multiple activating sequences spread N-constant region, to form at least five phosphorylated throughout the region.
    [Show full text]
  • Mechanisms of Wnt Signaling in Development
    P1: APR/ary P2: ARS/dat QC: ARS/APM T1: ARS August 29, 1998 9:42 Annual Reviews AR066-03 Annu. Rev. Cell Dev. Biol. 1998. 14:59–88 Copyright c 1998 by Annual Reviews. All rights reserved MECHANISMS OF WNT SIGNALING IN DEVELOPMENT Andreas Wodarz Institut f¨ur Genetik, Universit¨at D¨usseldorf, Universit¨atsstrasse 1, 40225 D¨usseldorf, Germany; e-mail: [email protected] Roel Nusse Howard Hughes Medical Institute and Department of Developmental Biology, Stanford University, Stanford, CA 94305-5428; e-mail: [email protected] KEY WORDS: Wnt, wingless, frizzled, catenin, signal transduction ABSTRACT Wnt genes encode a large family of secreted, cysteine-rich proteins that play key roles as intercellular signaling molecules in development. Genetic studies in Drosophila and Caenorhabditis elegans, ectopic gene expression in Xenopus, and gene knockouts in the mouse have demonstrated the involvement of Wnts in pro- cesses as diverse as segmentation, CNS patterning, and control of asymmetric cell divisions. The transduction of Wnt signals between cells proceeds in a complex series of events including post-translational modification and secretion of Wnts, binding to transmembrane receptors, activation of cytoplasmic effectors, and, finally, transcriptional regulation of target genes. Over the past two years our understanding of Wnt signaling has been substantially improved by the identifi- cation of Frizzled proteins as cell surface receptors for Wnts and by the finding that -catenin, a component downstream of the receptor, can translocate to the nucleus and function as a transcriptional activator. Here we review recent data that have started to unravel the mechanisms of Wnt signaling.
    [Show full text]
  • Mrg15 Stimulates Ash1 H3K36 Methyltransferase Activity and Facilitates Ash1 Trithorax Group Protein Function in Drosophila
    ARTICLE DOI: 10.1038/s41467-017-01897-3 OPEN Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila Chang Huang1, Fu Yang2, Zhuqiang Zhang1, Jing Zhang1, Gaihong Cai2, Lin Li2, Yong Zheng1, She Chen2, Rongwen Xi2 & Bing Zhu1,3 fi 1234567890 Ash1 is a Trithorax group protein that possesses H3K36-speci c histone methyltransferase activity, which antagonizes Polycomb silencing. Here we report the identification of two Ash1 complex subunits, Mrg15 and Nurf55. In vitro, Mrg15 stimulates the enzymatic activity of Ash1. In vivo, Mrg15 is recruited by Ash1 to their common targets, and Mrg15 reinforces Ash1 chromatin association and facilitates the proper deposition of H3K36me2. To dissect the functional role of Mrg15 in the context of the Ash1 complex, we identify an Ash1 point mutation (Ash1-R1288A) that displays a greatly attenuated interaction with Mrg15. Knock-in flies bearing this mutation display multiple homeotic transformation phenotypes, and these phenotypes are partially rescued by overexpressing the Mrg15-Nurf55 fusion protein, which stabilizes the association of Mrg15 with Ash1. In summary, Mrg15 is a subunit of the Ash1 complex, a stimulator of Ash1 enzymatic activity and a critical regulator of the TrxG protein function of Ash1 in Drosophila. 1 National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. 2 National institute of Biological Sciences, Beijing 102206, China. 3 College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China. Chang Huang, Fu Yang and Zhuqiang Zhang contributed equally to this work. Correspondence and requests for materials should be addressed to R.X.
    [Show full text]
  • Control of Tissue Morphogenesis by the HOX Gene Ultrabithorax Maria-Del-Carmen Diaz-De-La-Loza1, Ryan Loker2,3, Richard S
    © 2020. Published by The Company of Biologists Ltd | Development (2020) 147, dev184564. doi:10.1242/dev.184564 RESEARCH ARTICLE Control of tissue morphogenesis by the HOX gene Ultrabithorax Maria-del-Carmen Diaz-de-la-Loza1, Ryan Loker2,3, Richard S. Mann2,3 and Barry J. Thompson1,4,* ABSTRACT domain named the ‘homeobox’ that is found throughout the HOX Mutations in the Ultrabithorax (Ubx) gene cause homeotic family of transcription factors (Affolter et al., 1990a,b, 2008; Akam transformation of the normally two-winged Drosophila into a four- et al., 1984; Akam, 1983; Beachy et al., 1985; Bender et al., 1983; winged mutant fly. Ubx encodes a HOX family transcription factor that Casanova et al., 1985; Chan et al., 1994; Chan and Mann, 1993; specifies segment identity, including transformation of the second set Desplan et al., 1988; Gehring, 1992; Mann and Hogness, 1990; of wings into rudimentary halteres. Ubx is known to control the McGinnis et al., 1984a,b; Sánchez-Herrero et al., 1985; Scott and expression of many genes that regulate tissue growth and patterning, Weiner, 1984; Struhl, 1982). but how it regulates tissue morphogenesis to reshape the wing into a In Drosophila, mutations in Ubx alter the identity of an entire haltere is still unclear. Here, we show that Ubx acts by repressing the segment of the body plan, namely transformation of the third expression of two genes in the haltere, Stubble and Notopleural, both thoracic segment into a duplicated second thoracic segment of which encode transmembrane proteases that remodel the apical (Bridges, 1944; Lewis, 1963, 1978, 1998). Ubx is strongly extracellular matrix to promote wing morphogenesis.
    [Show full text]
  • Homeotic Gene Action in Embryonic Brain Development of Drosophila
    Development 125, 1579-1589 (1998) 1579 Printed in Great Britain © The Company of Biologists Limited 1998 DEV1254 Homeotic gene action in embryonic brain development of Drosophila Frank Hirth, Beate Hartmann and Heinrich Reichert* Institute of Zoology, University of Basel, Rheinsprung 9, CH-4051 Basel, Switzerland *Author for correspondence (e-mail: [email protected]) Accepted 18 February; published on WWW 1 April 1998 SUMMARY Studies in vertebrates show that homeotic genes are absence of labial, mutant cells are generated and positioned involved in axial patterning and in specifying segmental correctly in the brain, but these cells do not extend axons. identity of the embryonic hindbrain and spinal cord. To Additionally, extending axons of neighboring wild-type gain further insights into homeotic gene action during CNS neurons stop at the mutant domains or project ectopically, development, we here characterize the role of the homeotic and defective commissural and longitudinal pathways genes in embryonic brain development of Drosophila. We result. Immunocytochemical analysis demonstrates that first use neuroanatomical techniques to map the entire cells in the mutant domains do not express neuronal anteroposterior order of homeotic gene expression in the markers, indicating a complete lack of neuronal identity. Drosophila CNS, and demonstrate that this order is An alternative glial identity is not adopted by these mutant virtually identical in the CNS of Drosophila and mammals. cells. Comparable effects are seen in Deformed mutants but We then carry out a genetic analysis of the labial gene in not in other homeotic gene mutants. Our findings embryonic brain development. Our analysis shows that demonstrate that the action of the homeotic genes labial loss-of-function mutation and ubiquitous overexpression of and Deformed are required for neuronal differentiation in labial results in ectopic expression of neighboring the developing brain of Drosophila.
    [Show full text]
  • Homeotic Transformations and Limb Defects in Hox All Mutant Mice
    Downloaded from genesdev.cshlp.org on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press Homeotic transformations and limb defects in Hox All mutant mice Kersten M. Small and S. Steven Potter ~ Division of Basic Science Research, Children's Hospital Research Foundation, Cincinnati, Ohio 45229 USA Hox All is one of the expanded set of vertebrate homeo box (Hox) genes with similarities to the Drosophila homeotic gene, Abdominal-B (Abd-B). These Abd-B-type Hox genes have been shown to be expressed in the most caudal regions of the developing vertebrate embryo and in overlapping domains within the developing limbs, suggesting that these genes play important roles in pattern formation in both appendicular and axial regions of the body. In this report whole-mount in situ hybridization in mouse embryos gave a precise description of Hox All gene expression in the developing limbs and in the axial domain of the developing body. In addition, we generated a targeted mutation in Hox All and characterized the resulting phenotype to begin to dissect developmental functions of the Abd-B subfamily of Hox genes. Hox All mutant mice exhibited double homeotic transformations, with the thirteenth thoracic segment posteriorized to form an additional first lumbar vertebra and with the sacral region anteriorized, generating yet another lumbar segment. Furthermore, skeletal malformations were observed in both forelimbs and hindlimbs. In mutant forelimbs, the ulna and radius were misshapen, the pisiform and triangular carpal bones were fused, and abnormal sesamoid bone development occurred. In mutant hindlimbs the tibia and fibula were joined incorrectly and malformed at their distal ends.
    [Show full text]
  • Fusion of PAX3 to a Member of the Forkhead Family of Transcription Factors in Human Alveolar Rhabdomyosarcoma1
    [CANCER RESEARCH 53, 5108-5112. November 1. 1993] Advances in Brief Fusion of PAX3 to a Member of the Forkhead Family of Transcription Factors in Human Alveolar Rhabdomyosarcoma1 David N. Shapiro,2 Jack E. Sublett, Baitao Li, James R. Downing, and Clayton W. Naeve Departments of Experimental Oncology /I). N. S., J. E. S., B. L.¡.Hcmatology/Oncology ¡D.N. S./, Pathology [J. R. D.¡, Tumor Cell Biology /J. R. D./, anil Virology and Molecular Biology fC. W. N.¡,St. Jude Children's Research Hospital. Memphis. Tennessee 38105, and Departments of Pediatrics [D. N. S.¡and Pathology /./. R. D.. C. W. N.J, University of Tennessee College of Medicine. Memphis. Tennessee 38163 Abstract alveolar rhabdomyosarcoma and show that this rearrangement results in the creation of a chimeric fusion gene composed of 5' PAX3 Alveolar rhabdomyosarcoma, a malignant tumor of skeletal muscle, is sequences juxtaposed to 3' sequences derived from a previously un- characterized by a chromosomal translocation, t(2;13)(q35;ql4). This described member of the forkhead family of transcription factors, translocation Is associated with a structural rearrangement of the gene provisionally designated ALV (7). In PAX3-ALV, the putative 3' tran encoding /' 1 \ ¡.a presumed transcriptional regulator expressed exclu sively during embryogenesis. The breakpoint results in a fusion between scriptional activation domain of PAX3 is replaced by the bisected PAX3 and a gene provisionally named ALV, a novel member of the fork- forkhead binding domain of ALV, while retaining the structural integ head family of transcription factors. In PAX3-ALV, the structural integrity rity of the PAX3 paired box and homeodomain.
    [Show full text]
  • Evolutionary Developmental Biology Gene Regulation in Fruit Flies
    Evolutionary Developmental Gene regulation in fruit flies Biology • Maternal effect genes, which are genes in the mother’s genome for RNAs that are pumped into each egg cell, regulate. • gap genes, which determine large areas of the embryo, and which regulate. • pair-rule genes, which are expressed in alternating bands and specify the future segments of the embryo, and which regulate. • homeotic genes, which determine segment identity, and EVO DEVO which regulate. • realisator genes, which cause segment differentiation a.k.a. “EVO-DEVO” Drosophila egg, showing the location of the maternal Maternal genes mRNA bicoid (top) and the localization of the bicoid regulate gap genes; for protein, forming a gradient from the future head end example, bicoid (top) to the tail end regulates hunchback (middle, shown in orange) and Krüppel (middle, shown in green). Gap genes regulate pair-rule genes such as fushi tarazu (bottom). Both gap and pair-rule genes regulate homeotic genes. 1 Early-stage Drosophila embryo, stained to show the expression patterns of the pair-rule genes even- skipped (dark blue) and fushi tarazu (brown). Pair- rule genes regulate segment-polarity genes (which I Just a part of the ain’t getting’ into here) and homeotic genes. gene regulatory cascade, and we haven’t even got to the homeotic genes yet. Homeotic Genes Computer model of • Homeotic genes contain a 180-bp sequence the Ubx protein called a homeobox that codes for the DNA- (shown in gray) binding part of the protein (the homeodomain). binding to DNA (shown in orange). • Homeotic genes lay down segment identity This helix-turn-helix – As such, homeotic genes determine the placement protein interacts with of major structures RNA polymerase II to – For example: the homeotic gene Ultrabithorax, or control the expression Ubx, regulates a set of a dozen genes that of other genes.
    [Show full text]