Biology:Hunchback (gene)

From HandWiki
Short description: Maternal effect gene and gap gene
Hunchback (gene)
Identifiers
OrganismDrosophila melanogaster
Symbolhb
UniProtP05084

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.

Maternal (Top) and zygotic (Bottom) hunchback (hb) patterning and regulation.

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.[7][8][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.[11]

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.[11][13]

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,[12] 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

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. doi:10.1083/jcb.200601156. ISSN 1540-8140. PMID 16636144. PMC 2063813. https://doi.org/10.1083/jcb.200601156. 
  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. doi:10.1002/j.1460-2075.1988.tb03004.x. ISSN 0261-4189. PMID 2901954. PMC 457163. http://dx.doi.org/10.1002/j.1460-2075.1988.tb03004.x. 
  3. ↑ Wang, Charlotte; Lehmann, Ruth (1991). "Nanos is the localized posterior determinant in Drosophila". Cell 66 (4): 637–647. doi:10.1016/0092-8674(91)90110-k. ISSN 0092-8674. PMID 1908748. https://doi.org/10.1016/0092-8674(91)90110-K. 
  4. ↑ Gavis, Elizabeth R.; Lehmann, Ruth (1992). "Localization of nanos RNA controls embryonic polarity". Cell 71 (2): 301–313. doi:10.1016/0092-8674(92)90358-j. ISSN 0092-8674. PMID 1423595. http://dx.doi.org/10.1016/0092-8674(92)90358-j. 
  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" (in en). Nature 327 (6121): 383–389. doi:10.1038/327383a0. ISSN 1476-4687. https://www.nature.com/articles/327383a0. 
  6. ↑ Irish, Vivian; Lehmann, Ruth; Akam, Michael (1989). "The Drosophila posterior-group gene nanos functions by repressing hunchback activity" (in en). Nature 338 (6217): 646–648. doi:10.1038/338646a0. ISSN 1476-4687. PMID 2704419. Bibcode: 1989Natur.338..646I. https://www.nature.com/articles/338646a0. 
  7. ↑ 7.0 7.1 Driever, Wolfgang; Nüsslein-Volhard, Christiane (1989). "The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo" (in en). Nature 337 (6203): 138–143. doi:10.1038/337138a0. ISSN 1476-4687. PMID 2911348. Bibcode: 1989Natur.337..138D. https://www.nature.com/articles/337138a0. 
  8. ↑ 8.0 8.1 Perry, Michael W.; Boettiger, Alistair N.; Levine, Michael (2011-08-16). "Multiple enhancers ensure precision of gap gene-expression patterns in the Drosophila embryo" (in en). Proceedings of the National Academy of Sciences 108 (33): 13570–13575. doi:10.1073/pnas.1109873108. ISSN 0027-8424. PMID 21825127. Bibcode: 2011PNAS..10813570P. 
  9. ↑ Struhl, Gary; Struhl, Kevin; Macdonald, Paul M. (1989). "The gradient morphogen bicoid is a concentration-dependent transcriptional activator". Cell 57 (7): 1259–1273. doi:10.1016/0092-8674(89)90062-7. ISSN 0092-8674. PMID 2567637. https://doi.org/10.1016/0092-8674(89)90062-7. 
  10. ↑ Perry, M.; Bothma, J.; Luu, R.; Levine, M. (2012). "Precision of Hunchback Expression in the Drosophila Embryo". Current Biology 22 (23): 2247–2252. doi:10.1016/j.cub.2012.09.051. ISSN 0960-9822. PMID 23122844. PMC 4257490. https://doi.org/10.1016/j.cub.2012.09.051. 
  11. ↑ 11.0 11.1 11.2 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. doi:10.1242/dev.121.9.3067. ISSN 0950-1991. PMID 7555732. https://doi.org/10.1242/dev.121.9.3067. 
  12. ↑ 12.0 12.1 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. et al. (2018-09-07). "Hunchback is counter-repressed to regulate even-skipped stripe 2 expression in Drosophila embryos" (in en). PLOS Genetics 14 (9): e1007644. doi:10.1371/journal.pgen.1007644. ISSN 1553-7404. PMID 30192762. 
  13. ↑ 13.0 13.1 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. doi:10.1016/0012-1606(87)90045-5. ISSN 0012-1606. PMID 3803711. https://dx.doi.org/10.1016/0012-1606%2887%2990045-5. 
  14. ↑ Schröder, C.; Tautz, D.; Seifert, E.; Jäckle, H. (1988). "Differential regulation of the two transcripts from the Drosophila gap segmentation gene hunchback." (in en). The EMBO Journal 7 (9): 2881–2887. doi:10.1002/j.1460-2075.1988.tb03145.x. PMID 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" (in en). Nature 346 (6284): 577–580. doi:10.1038/346577a0. ISSN 1476-4687. PMID 2377231. Bibcode: 1990Natur.346..577H. https://www.nature.com/articles/346577a0. 
  16. ↑ Gaul, Urike; Jäckle, Herbert (1989). "Analysis of maternal effect mutant combinations elucidates regulation and function of the overlap of hunchback and Krüppel gene expression in the Drosophila blastoderm embryo". Development 107 (3): 651–662. doi:10.1242/dev.107.3.651. PMID 2612383. https://journals.biologists.com/dev/article/107/3/651/36537/Analysis-of-maternal-effect-mutant-combinations. Retrieved 2023-12-04. 
  17. ↑ Small, S.; Kraut, R.; Hoey, T.; Warrior, R.; Levine, M. (1991-05-01). "Transcriptional regulation of a pair-rule stripe in Drosophila." (in en). Genes & Development 5 (5): 827–839. doi:10.1101/gad.5.5.827. ISSN 0890-9369. PMID 2026328. http://genesdev.cshlp.org/content/5/5/827. 
  18. ↑ Clark, Erik (2017-09-27). "Dynamic patterning by the Drosophila pair-rule network reconciles long-germ and short-germ segmentation" (in en). PLOS Biology 15 (9): e2002439. doi:10.1371/journal.pbio.2002439. ISSN 1545-7885. PMID 28953896. 
  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. doi:10.1016/j.ydbio.2009.12.013. ISSN 0012-1606. PMID 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. doi:10.4049/jimmunol.0802372. ISSN 0022-1767. PMID 19342657. https://doi.org/10.4049/jimmunol.0802372. 
  21. ↑ Lentaigne, Claire et al. (2019). "Germline mutations in the transcription factor IKZF5 cause thrombocytopenia". Blood 134 (23): 2070–2081. doi:10.1182/blood.2019000782. PMID 31217188. https://ashpublications.org/blood/article/134/23/2070/374927/Germline-mutations-in-the-transcription-factor. Retrieved 2023-12-04. 
  22. ↑ Wang, Yang; Cheng, Wenyan; Zhang, Yvyin; Zhang, Yuliang; Sun, Tengfei; Zhu, Yongmei; Yin, Wei; Zhang, Jianan et al. (2023). "Identification of IKZF1 genetic mutations as new molecular subtypes in acute myeloid leukaemia" (in en). Clinical and Translational Medicine 13 (6): e1309. doi:10.1002/ctm2.1309. ISSN 2001-1326. PMID 37345307. 
  23. ↑ Tran, K; Miller, M; Doe, C (2010). "Recombineering Hunchback identifies two conserved domains required to maintain neuroblast competence and specify early-born neuronal identity". Development 137 (9): 1421–1430. doi:10.1242/dev.048678. PMID 20335359. PMC 2853844. https://journals.biologists.com/dev/article/137/9/1421/44264/Recombineering-Hunchback-identifies-two-conserved. Retrieved 2023-12-04. 
  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" (in en). Scientific Reports 13 (1): 8458. doi:10.1038/s41598-023-35609-3. ISSN 2045-2322. PMID 37231055. Bibcode: 2023NatSR..13.8458P. 



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