Drosophila Embryo: Homeotic Genes in Specification of the Anterior–Posterior Axis

Abstract

Embryonic expression of homeotic genes in Drosophila melanogaster imparts the diversity of morphology and cell type along the anterior–posterior axis that is characteristic of its body plan. The homeotic genes encode a related set of nine transcription factors. Each homeotic gene has a unique, temporally dynamic expression pattern, battery of target genes and range of regulatory effects. Changes in any of these three aspects can have dramatic consequences due to the large number of target genes affected. These dramatic effects place the homeotic genes high in the regulatory gene hierarchy of developmental programmes and are sometimes referred to as ‘master regulators’ of identity. The combined action of all nine genes produces a unique cellular pattern of gene activation and repression across the embryo that changes throughout development. The result is the specification of the diverse cells and tissues typical of the animal body in the precise pattern that gives each segment or region its own identity.

Key Concepts

  • Mutations in Hox genes alter their modulation of underlying developmental programmes and produce homeotic transformations.
  • The Hox genes of Drosophila melanogaster are organised into two complexes that arose from a single ancestral complex.
  • The variation among Hox genes limits the diversity of segment‐specific development.
  • HOX proteins are transcription factors that bind DNA via the homeodomain which is encoded by the homeobox.
  • Homeoboxes and homeodomain proteins form a superfamily of which the Hox genes are a small part.
  • Hox expression and segmentation are initiated by the same regulatory cascade, insuring proper domains of Hox expression.
  • An important aspect of Hox expression is that it is not static but continually changing during development.
  • Initiation of Hox expression requires different factors than their maintenance, which depends on the chromatin structure.
  • By regulating the expression of other regulators such as selector and signal transducing genes, Hox genes greatly magnify the number of genes under their control.
  • Segmental identity is a consequence of a unique combination of Hox‐regulated events achieved by the dynamic and diverse temporal and spatial expression of Hox genes and the specific target recognition and regulation capabilities of each Hox protein.

Keywords: Hox; embryogenesis; homeotic; homeodomain; segmental identity

Figure 1. The organisation and expression of Hox genes in Drosophila melanogaster. The diagram shows the embryonic expression pattern and phenotypic result for the nine Hox genes. The relative chromosomal positions of the ANT‐C and BX‐C genes are shown at the bottom. The expression of each gene in a D. melanogaster embryo is shown as a colour‐coded line and shading. The lines represent the approximate extent of metameric expression domains. The shading in the embryo is representative of modulated expression patterns but is not intended to accurately depict any specific time during development. A diagram of a first instar larva shows the diverse segmental identities produced by Hox gene expression. Ic, intercalary; Mn, mandibular; Mx, maxillary; Lb, labial; dr, dorsal ridge; T1, first thoracic; A1, first abdominal; A8, eighth abdominal; ps, posterior spiracle.
Figure 2. The Hox homeodomains. The aligned sequences of homeodomains and flanking amino acids are shown using one‐letter amino acid (AA) code. The helices of the homeodomain and YPWM motif are marked. Dashes represent spaces introduced into the sequence to make the alignment, and dots represent amino acids not shown. The Abd‐B and zen homeodomains are shown separate because of their divergent homeodomains. Asterisks along the top indicate identical amino acids for the top seven homeodomains. Asterisks along the bottom mark identical amino acids for all nine homeodomains.
Figure 3. How Hox genes specify multiple segment identities. Shown is a schematic of the region of the Drosophila melanogaster embryo from the labial segment (Lb), through the three thoracic segments (T1, T2 and T3) and first abdominal segment (A1). The region is also labelled in parasegments (PS3–6), and the grooves between units represent parasegmental borders at this time. Dorsal is up, and ventral is down. In addition to the three Hox genes, Scr, Antp and Ubx, the position genes (coordinate, gap and pair rule), two region‐specific developmental programmes and the segment polarity genes are shown. A trunk programme is represented by tsh. There is also a gnathal programme indicated. (a) At the Hox initiation phase, all genes receive positional information from the position genes and begin to express in crude domains. The domains are colour coded. Gnathal (dark green), Scr (green), tsh (red), Antp (yellow), Ubx (blue) and segment polarity (purple). Arrows represent activation, and terminal blocks represent repression or modulation. Lines drawn between gene labels represent regulatory interactions between genes. Lines drawn to features represent regulatory events within a developmental pathway. (b) At the Hox metameric phase, the position genes and segment polarity genes provide the positional information needed to complete the metameric pattern. The gnathal identity gene(s) are expressed in the labial segment and alter the developmental possibilities to include gnathal identity. Scr is expressed in the labial segment and promotes gnathal development by repressing tsh in the labial segment. Ubx promotes abdominal development by activating tsh and repressing Antp and Scr, and blocking the formation of the T3 spiracle. tsh expression sets in motion several developmental programmes for the trunk segments including spiracle (oval), appendage primordia (circle) and dorsal and ventral pits (dots). Open shapes represent pattern elements where primordia (filled shapes) will form. (c) At the early modulated phase of Hox expression, gnathal and Scr expression have combined to activate a labial appendage primordia including adult labial palp (ventral oval in Lb). The spiracle (dorsal vertical ovals ) and appendage (ventral ovals) programmes are initiated in the trunk. In PS6, the spiracle is suppressed by Ubx, and the pits (black dots) are converted to an abdominal sensory hair (red dots). Ubx and Scr expand their expression domain towards T2. Positional information is no longer available. (d) At the late modulated phase of Hox expression, while the dorsal pits in T2 and T3 begin to migrate more ventrally, Scr activity prevents the migration of the pit in T1. Ubx expression blocks formation of the T2 spiracle Note that the overt segmentation of the embryo has become segmental in register. (e) Between late modulated phase of Hox expression and hatching, Scr expression produces a labial sense organ (blue with white dots) from the appendage primordia in the labial segment. In the thorax, tsh and Scr stimulate the segment polarity genes to put down lightweight denticle rows (indicated by the ventral triangles) and elaborate a denticle ‘beard’ (second denticle band) and anterior denticle band in T1. Antp suppresses the formation of additional beards and dictates a slightly heavier set of denticles. Ubx commands the heaviest set of denticles in T3 and A1. All denticle bands require the action of the segment polarity genes. Scr expression in the imaginal disc will prevent the formation of a dorsal appendage (wing) in T1, and Ubx will alter the development of the dorsal appendage to produce a haltere rather than a wing in T3. Regulatory interactions between genes are not shown to reduce the complexity of the diagram. (f) At hatching, there are five unique segments. (1) The labial segment contains a labial sense organ (blue circle) and an imaginal disc with no dorsal appendage primordia (not shown). (2) The first thoracic segment contains a spiracle (dorsal oval), unmigrated pits (dots), a larval appendage (ventral circle), denticle bands with beard (triangles) and an imaginal disc with no dorsal appendage primordia (not shown). (3) The second thoracic segment contains migrated pits (dots), a larval appendage (ventral circle) and an imaginal disc with a dorsal wing primordia (not shown). (4) The third thoracic segment has migrated pits, thicker denticles, larval appendage and an imaginal disc with a dorsal haltere primordia (not shown). (5) The first abdominal segment contains abdominal‐type denticles and sensory hairs (red dots).
close

References

Agrawal P, Habib F, Yelagandula R (2011) Genome-level identification of targets of Hox protein Ultrabithorax in Drosophila: novel mechanisms for target selection. Sci Rep 1: 205. DOI: https://doi.org/10.1038/srep00205.

Akam M (1989) Hox and HOM: homologous gene clusters in insects and vertebrates. Cell 57: 347–349.

Akam M (1998) Hox genes, homeosis and the evolution of segment identity: no need for hopeless monsters. International Journal of Developmental Biology 42: 445–451.

Andrew DJ, Horner MA, Petitt MG, Smolik SM and Scott MP (1994) Setting limits on homeotic gene function: restraint of Sex combs reduced activity by teashirt and other homeotic genes. EMBO Journal 13: 1132–1144.

Bate M and Martinez‐Arias A (eds) (1993) The Development of Drosophila melanogaster. Cold Spring Harbor Laboratory Press: New York, NY.

Bergson C and McGinnis W (1990) An autoregulatory enhancer element of the Drosophila homeotic gene Deformed. The EMBO Journal 9 (13): 4287–4297.

Bienz M (1994) Homeotic genes and positional signalling in the Drosophila viscera. Trends in Genetics 10: 22–26.

Castelli‐Gair JE and Akam M (1995) How the Hox gene Ultrabithorax specifies two different segments: the significance of spatial and temporal regulation within metameres. Development 121: 2973–2982.

Chouinard S and Kaufman TC (1991) Control of expression of the homeotic labial (lab) locus of Drosophila melanogaster: evidence for both positive and negative autogenous regulation. Development 113: 1267–1280.

Galant R, Walsh CM and Carroll SB (2002) Hox repression of a target gene: extradenticle‐independent, additive action through multiple monomer binding sites. Development 129: 3115–3126.

Garcia‐bellido A (1977) Homoeotic and atavic mutations in insects. American Zoologist 17: 613–629.

Gebelein B, McKay D and Mann R (2004) Direct integration of Hox and segmentation gene inputs during Drosophila development. Nature 431: 653–659.

Gellon G and McGinnis W (1998) Shaping animal body plans in development and evolution by modulation of Hox expression patterns. BioEssays 20: 116–125.

Gorman MJ and Kaufman TC (1995) Genetic analysis of embryonic &acting regulatory elements of the Drosophila homeotic gene sex combs reduced. Genetics 140: 557–572.

Hayes PH, Takashi T and Denell RE (1984) Homoeosis in Drosophila: the Ultrabithorax larval syndrome. Proceedings of the National Academy of Sciences of the United States of America 81: 545–549.

Hoppler S and Bienz M (1994) Specification of a single cell type by a Drosophila homeotic gene. Cell 76: 689–702.

Jack TP and McGinnis W (1990) Establishment of the Deformed expression stripe requires the combinatorial action of coordinate, gap and pair‐rule proteins. EMBO Journal 9: 1187–1198.

Kasis JA, Kennison JA and Tamkun JW (2018) Polycomb and Trithorax Group Genes in Drosophila. Genetics 206 4: 1699–1725. DOI: https://doi.org/10.1534/genetics.115.185116.

Kaufman TC, Lewis R and Wakimoto B (1980) Cytogenetic analysis of chromosome 3 in Drosophila melanogaster: the homeotic gene complex in polytene chromosome interval 84 A‐B. Genetics 94: 115–133.

Kennison JA (2015) The Polycomb And Trithorax Group Proteins Of Drosophila: Trans‐Regulators of Homeotic Gene Function. Annual Review of Genetics Vol. 29: 289–303. DOI: https://doi.org/10.1146/annurev.ge.29.120195.001445.

Kukalova‐Peck J (1978) Origin and evolution of insect wings and their relation to metamorphosis, as documented by the fossil record. Journal of Morphology 156: 53–126.

Kuziora MA and McGinnis W (1988) Different transcripts of the Drosophila Abd‐B gene correlate with distinct genetic sub‐functions. EMBO Journal 7: 3233–3244.

Kyrchanova O, Mogila V, Wolle D, et al. (2015) The boundary paradox in the Bithorax complex. Mechanisms of Development 138: 122–132.

Lewis EB (1978) A gene complex controlling segmentation in Drosophila. Nature 276: 565–570.

Lewis EB (1994) Homeosis: the first 100 years. Trends in Genetics 10: 341–343.

Lindsley DL and Zimm GG (1990) The Genome of Drosophila melanogaster. Academic Press: New York, NY.

Maeda RK and Karch F (2006) The ABC of the BX‐C: the bithorax complex explained. Development 133: 1413–1422. DOI: 10.1242/dev.02323.

Mahaffey JW, Diederich RJ and Kaufman TC (1989) Novel patterns of homeotic protein accumulation in the head of the Drosophila embryo. Development 105: 167–174.

Mallo M and Alonso CR (2013) The regulation of Hox gene expression during animal development. Development 140: 3951–3963.

Mann RS and Affolter M (1998) Hox proteins meet more partners. Current Opinion in Genetics and Development 8: 423–429.

McGinnis W and Krumlauf R (1992) Homeobox genes and axial patterning. Cell 68 (2): 283–302.

McGinnis N, Ragnhildstveit E, Veraksa A and McGinnis W (1998) A cap ‘n’ collar protein isoform contains a selective Hox repressor function. Development 125: 4553–4564.

Michelson AM (1994) Muscle pattern diversification in Drosophila is determined by the autonomous function of homeotic genes in the embryonic mesoderm. Development 120: 755–768.

Miller DFB, Holtzman SL, Kalkbrenner A and Kaufman TC (2001) Homeotic complex (Hox) gene regulation and homeosis in the mesoderm of the Drosophila melanogaster embryo: the roles of signal transduction and cell autonomous regulation. Mechanisms of Development 102: 17–32.

Morata G (1993) Homeotic genes of Drosophila. Current Opinions in Genetics and Development 3: 606–614.

Nusslein‐Volhard CWE (1980) Mutations affecting segment number and polarity in Drosophila. Nature 287: 795–801.

Pavlopoulos A and Akam M (2011) Hox gene Ultrabithorax regulates distinct sets of target genes at successive stages of Drosophila haltere morphogenesis. Proceedings of the National Academy of Sciences of the United States of America 108 (7): 2855–2860.

Pearson JC, Lemons D and McGinnis W (2005) Modulating Hox gene functions during animal body patterning. Nature Reviews Genetics 6: 893–904.

Pederson JD, Kiehart DP and Mahaffey JW (1996) The role of HOM‐C Genes in segmental transformations: reexamination of the Drosophila Sex combs reduced embryonic phenotype. Developmental Biology 180: 131–142.

Prokop A, Bray S, Harrison E and Technau GM (1998) Homeotic regulation of segment‐specific differences in neuroblast numbers and proliferation in the Drosophila central nervous system. Mechanisms of Development 74: 99–110.

Röder L, Vola C and Kerridge S (1992) The role of the teashirt gene in trunk segmental identity in Drosophila. Development 115: 1017–1033.

Rogers BT, Peterson MD and Kaufman TC (1997) Evolution of the insect body plan as revealed by the Sex combs reduced expression pattern. Development 124: 149–157.

Struhl G and White RAH (1985) Regulation of the Ultrabithorax gene of Drosophila by the other Bithorax‐complex genes. Cell 43: 507–519.

Triesman J, Harris E, Wilson D and Desplan C (1992) The homeodomain: a new face for the helix‐turn‐helix? BioEssays 14: 145–150.

Warren R, Nagy L, Selegue J and Carroll (1994) Evolution of homeotic gene regulation and function in flies and butterflies. Nature 372: 458–461.

White R and Wilcox M (1985) Regulation of the distribution of Ultrabithorax proteins in Drosophila. Nature 318: 563–567.

Further Reading

Castelli‐Gair J, Grieg S, Micklem G and Akam M (1994) Dissecting the temporal requirements for homeotic gene function. Development 120: 1982–1995.

Diaz‐de‐la‐Loza M, Loker R, Mann RS, et al. (2020) Control of tissue morphogenesis by the HOX gene Ultrabithorax. Development 147: dev184564. DOI: 10.1242/dev.184564.

Kaschula R, Pinho S and Alonso CR (2018) MicroRNA‐dependent regulation of Hox gene expression sculpts fine‐grain morphological patterns in a Drosophila appendage. Development 145: dev161133. DOI: 10.1242/dev.161133.

Kingsolver JG and Koehl MAR (1994) Selective factors in the evolution of insect wings. Annual Review of Entomology 39: 425–451.

Lin Q, Lin L and Zhou J (2010) Chromatin insulator and the promoter targeting sequence modulate the timing of long‐range enhancer–promoter interactions in the Drosophila embryo. Developmental Biology 339: 329–337.

McGinnis W (1994) A century of homeosis, a decade of homeoboxes. Genetics 137: 607–611.

Schmitt S, Prestel M and Paro R (2005) Intergenic transcription through a polycomb group response element counteracts silencing. Genes & Development 19: 697–708.

Zouaz A, Auradkar A, Delfini MC, et al. (2017) The Hox proteins Ubx and AbdA collaborate with the transcription pausing factor M1BP to regulate gene transcription. The EMBO Journal 36: 2887–2906.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Rogers, Bryan T(Oct 2020) Drosophila Embryo: Homeotic Genes in Specification of the Anterior–Posterior Axis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0029210]