Hunchback (gene) explained

Symbol:hb
Uniprot:P05084
Organism:Drosophila melanogaster

Hunchback is a maternal effect and zygotic gene expressed in the embryos of the fruit fly Drosophila melanogaster. In maternal effect genes, the RNA or protein from the mother’s gene is deposited into the oocyte or embryo before the embryo can express its own zygotic genes.

Hunchback is a morphogen, meaning the concentration gradient of Hunchback at a specific region determines the segment or body part it develops into. This is possible because Hunchback is a transcription factor protein that binds to genes’ regulatory regions, changing RNA expression levels.

Hunchback expression pathway

Maternal Hunchback RNA enters the embryo at the syncytial blastoderm stage, where the entire embryo has undergone many nuclear divisions but has one communal cytoplasm,[1] allowing for RNA to disperse freely throughout the embryo. This allows the maternal effect genes Hunchback, Bicoid, Nanos, and Caudal to regulate zygotic genes to create different identities for different regions of the body.

The first step is establishing the anterior and posterior regions, which later give rise to the respective head and abdomen. In the syncytial blastoderm, Bicoid and Nanos RNA bind to protein ropes involved in cellular locomotion and intracellular transport called microtubules that ferry the RNA to the anterior and posterior regions, respectively.[2] [3] [4] Hunchback does not bind to microtubules and therefore diffuses uniformly throughout the embryo.[5] However, Nanos represses the translation of the Hunchback protein. Since Nanos is ferried to the posterior pole, maternal Hunchback is expressed predominantly in the anterior pole.[6]  

Hunchback is also expressed zygotically in the farmost anterior and posterior poles of the syncytial blastoderm. Anterior zygotic Hunchback expression is controlled by enhancers, regions of DNA that increase gene expression when transcription factors are bound. One enhancer is close to Hunchback,[7] and a recently discovered enhancer is farther away.[8] When Bicoid binds to these enhancers, the expression of Hunchback increases proportionally to the Bicoid concentration in the anterior pole.[9] [10] A separate regulatory region downstream of the Hunchback enhancers governs the posterior expression of zygotic Hunchback.[11] Here, Hunchback expression is proportional to the concentration of Tailless and Huckebein proteins available to bind to the regulatory region.

Effects of Hunchback expression

As a bifunctional transcription factor, Hunchback both activates and represses its target segmentation genes,[12] and in doing so, regulates the anterior and posterior embryonic segmentation in the Drosophila embryo.[13] [14] For example, anterior Hunchback expression is known to establish the region that later develops into the thoracic and jaw- and mouth-related segments, and posterior Hunchback expression for the development of abdominal segments.

Hunchback’s morphogenetic gradient regulates the expression of other gap genes, Krüppel and Knirps, wherein maternal Hunchback expression defines the anterior Knirps and posterior Krüppel borders, while zygotic Hunchback expression establishes the anterior Knirps border.[15]

Hunchback also establishes the expression pattern of pair-rule genes,[16] [17] such as even-skipped, expressed later in development to define distinct segments along the anterior-posterior axis. Pair-rule genes then encode transcription factors that regulate segment polarity genes: the final, most specified group of proteins that coordinate segmentation.[18]

Clinical significance

The Hunchback gene has a known human ortholog that evolved from a common ancestor, the Pegasus gene (Ikzf5) of the Ikaros family zinc finger group.[19] [20] Ikaros family genes encode transcription factors that have implications in thrombocytopenia, a blood clotting deficiency,[21] acute myeloid leukemia, a blood and bone marrow cancer,[22] and are involved in mammalian retinal and immune system development.[23] Ikaros family genes have also been implicated as an indicator for chronic graft-versus-host disease, a condition where immune cells attack transplanted tissue.[24]

See also

Notes and References

  1. Frescas . David . Mavrakis . Manos . Lorenz . Holger . DeLotto . Robert . Lippincott-Schwartz . Jennifer . 2006-04-24 . The secretory membrane system in the Drosophila syncytial blastoderm embryo exists as functionally compartmentalized units around individual nuclei . The Journal of Cell Biology . 173 . 2 . 219–230 . 10.1083/jcb.200601156 . 1540-8140 . 2063813 . 16636144.
  2. Berleth . T. . Burri . M. . Thoma . G. . Bopp . D. . Richstein . S. . Frigerio . G. . Noll . M. . Nüsslein-Volhard . C. . 1988 . The role of localization of bicoid RNA in organizing the anterior pattern of the Drosophila embryo. . The EMBO Journal . 7 . 6 . 1749–1756 . 10.1002/j.1460-2075.1988.tb03004.x . 2901954 . 19840074 . 0261-4189. free . 457163 .
  3. Wang . Charlotte . Lehmann . Ruth . 1991 . Nanos is the localized posterior determinant in Drosophila . Cell . 66 . 4 . 637–647 . 10.1016/0092-8674(91)90110-k . 1908748 . 37042131 . 0092-8674.
  4. Gavis . Elizabeth R. . Lehmann . Ruth . 1992 . Localization of nanos RNA controls embryonic polarity . Cell . 71 . 2 . 301–313 . 10.1016/0092-8674(92)90358-j . 1423595 . 8144448 . 0092-8674.
  5. Tautz . Diethard . Lehmann . Ruth . Schnürch . Harald . Schuh . Reinhard . Seifert . Eveline . Kienlin . Andrea . Jones . Keith . Jäckle . Herbert . 1987 . Finger protein of novel structure encoded by hunchback, a second member of the gap class of Drosophila segmentation genes . Nature . en . 327 . 6121 . 383–389 . 10.1038/327383a0 . 4263443 . 1476-4687.
  6. Irish . Vivian . Lehmann . Ruth . Akam . Michael . 1989 . The Drosophila posterior-group gene nanos functions by repressing hunchback activity . Nature . en . 338 . 6217 . 646–648 . 10.1038/338646a0 . 2704419 . 1989Natur.338..646I . 4267223 . 1476-4687.
  7. Driever . Wolfgang . Nüsslein-Volhard . Christiane . 1989 . The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo . Nature . en . 337 . 6203 . 138–143 . 10.1038/337138a0 . 2911348 . 1989Natur.337..138D . 29812 . 1476-4687.
  8. Perry . Michael W. . Boettiger . Alistair N. . Levine . Michael . 2011-08-16 . Multiple enhancers ensure precision of gap gene-expression patterns in the Drosophila embryo . Proceedings of the National Academy of Sciences . en . 108 . 33 . 13570–13575 . 10.1073/pnas.1109873108 . 0027-8424 . 3158186 . 21825127 . 2011PNAS..10813570P . free .
  9. Struhl . Gary . Struhl . Kevin . Macdonald . Paul M. . 1989 . The gradient morphogen bicoid is a concentration-dependent transcriptional activator . Cell . 57 . 7 . 1259–1273 . 10.1016/0092-8674(89)90062-7 . 2567637 . 35937518 . 0092-8674. free .
  10. Perry . M. . Bothma . J. . Luu . R. . Levine . M. . 2012 . Precision of Hunchback Expression in the Drosophila Embryo . Current Biology . 22 . 23 . 2247–2252 . 10.1016/j.cub.2012.09.051 . 0960-9822 . 4257490 . 23122844. 2012CBio...22.2247P .
  11. Margolis . Jonathan S. . Borowsky . Mark L. . SteingrÍmsson . EirÍkur . Shim . Chung Wha . Lengyel . Judith A. . Posakony . James W. . 1995-09-01 . Posterior stripe expression of hunchback is driven from two promoters by a common enhancer element . Development . 121 . 9 . 3067–3077 . 10.1242/dev.121.9.3067 . 7555732 . 0950-1991.
  12. Vincent . Ben J. . Staller . Max V. . Lopez-Rivera . Francheska . Bragdon . Meghan D. J. . Pym . Edward C. G. . Biette . Kelly M. . Wunderlich . Zeba . Harden . Timothy T. . Estrada . Javier . DePace . Angela H. . 2018-09-07 . Hunchback is counter-repressed to regulate even-skipped stripe 2 expression in Drosophila embryos . PLOS Genetics . en . 14 . 9 . e1007644 . 10.1371/journal.pgen.1007644 . 1553-7404 . 6145585 . 30192762 . free .
  13. Lehmann . Ruth . Nüsslein-Volhard . Christiane . 1987-02-01 . hunchback, a gene required for segmentation of an anterior and posterior region of the Drosophila embryo . Developmental Biology . 119 . 2 . 402–417 . 10.1016/0012-1606(87)90045-5 . 3803711 . 0012-1606.
  14. Schröder . C. . Tautz . D. . Seifert . E. . Jäckle . H. . 1988 . Differential regulation of the two transcripts from the Drosophila gap segmentation gene hunchback. . The EMBO Journal . en . 7 . 9 . 2881–2887 . 10.1002/j.1460-2075.1988.tb03145.x . 457082 . 2846287.
  15. Hülskamp . Martin . Pfeifle . Christine . Tautz . Diethard . 1990 . A morphogenetic gradient of hunchback protein organizes the expression of the gap genes Krüppel and knirps in the early Drosophila embryo . Nature . en . 346 . 6284 . 577–580 . 10.1038/346577a0 . 2377231 . 1990Natur.346..577H . 4304789 . 1476-4687.
  16. Gaul . Urike . Jäckle . Herbert . Analysis of maternal effect mutant combinations elucidates regulation and function of the overlap of hunchback and Krüppel gene expression in the Drosophila blastoderm embryo . 2023-12-04 . Development . 1989 . 107 . 3 . 651–662 . 10.1242/dev.107.3.651. 2612383 .
  17. Small . S. . Kraut . R. . Hoey . T. . Warrior . R. . Levine . M. . 1991-05-01 . Transcriptional regulation of a pair-rule stripe in Drosophila. . Genes & Development . en . 5 . 5 . 827–839 . 10.1101/gad.5.5.827 . 0890-9369 . 2026328. free .
  18. Clark . Erik . 2017-09-27 . Dynamic patterning by the Drosophila pair-rule network reconciles long-germ and short-germ segmentation . PLOS Biology . en . 15 . 9 . e2002439 . 10.1371/journal.pbio.2002439 . 1545-7885 . 5633203 . 28953896 . free .
  19. Large . Edward E. . Mathies . Laura D. . 2010-03-01 . hunchback and Ikaros-like zinc finger genes control reproductive system development in Caenorhabditis elegans . Developmental Biology . 339 . 1 . 51–64 . 10.1016/j.ydbio.2009.12.013 . 0012-1606 . 3721651 . 20026024.
  20. John . Liza B. . Yoong . Simon . Ward . Alister C. . 2009-04-15 . Evolution of the Ikaros Gene Family: Implications for the Origins of Adaptive Immunity . The Journal of Immunology . 182 . 8 . 4792–4799 . 10.4049/jimmunol.0802372 . 19342657 . 23682626 . 0022-1767. free . 10536/DRO/DU:30029773 . free .
  21. Germline mutations in the transcription factor IKZF5 cause thrombocytopenia . 2023-12-04 . Blood . 2019 . 10.1182/blood.2019000782 . Lentaigne . Claire . Greene . Daniel . Sivapalaratnam . Suthesh . Favier . Remi . Seyres . Denis . Thys . Chantal . Grassi . Luigi . Mangles . Sarah . Sibson . Keith . Stubbs . Matthew . Burden . Frances . Bordet . Jean-Claude . Armari-Alla . Corinne . Erber . Wendy . Farrow . Samantha . Gleadall . Nicholas . Gomez . Keith . Megy . Karyn . Papadia . Sofia . Penkett . Christopher J. . Sims . Matthew C. . Stefanucci . Luca . Stephens . Jonathan C. . Read . Randy J. . Stirrups . Kathleen E. . Ouwehand . Willem H. . Laffan . Michael A. . Frontini . Mattia . Freson . Kathleen . Turro . Ernest . 1 . 134 . 23 . 2070–2081 . 31217188 . 195193084 . free . 10044/1/71571 . free .
  22. Wang . Yang . Cheng . Wenyan . Zhang . Yvyin . Zhang . Yuliang . Sun . Tengfei . Zhu . Yongmei . Yin . Wei . Zhang . Jianan . Li . Jianfeng . Shen . Yang . 2023 . Identification of IKZF1 genetic mutations as new molecular subtypes in acute myeloid leukaemia . Clinical and Translational Medicine . en . 13 . 6 . e1309 . 10.1002/ctm2.1309 . 2001-1326 . 10285267 . 37345307.
  23. Tran . K . Miller . M . Doe . C . Recombineering Hunchback identifies two conserved domains required to maintain neuroblast competence and specify early-born neuronal identity . 2023-12-04 . Development . 2010 . 137 . 9 . 1421–1430 . 10.1242/dev.048678 . 2853844 . 20335359.
  24. Pereira . A. D. . de Molla . V. C. . Fonseca . A. R. B. M. . Tucunduva . L. . Novis . Y. . Pires . M. S. . Popi . A. F. . Arrais-Rodrigues . C. A. . 2023-05-25 . Ikaros expression is associated with an increased risk of chronic graft-versus-host disease . Scientific Reports . en . 13 . 1 . 8458 . 10.1038/s41598-023-35609-3 . 2045-2322 . 10212984 . 37231055. 2023NatSR..13.8458P .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Hunchback (gene)".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.