• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Aug 2004; 167(4): 1721–1737.
PMCID: PMC1471003

Dynamical analysis of regulatory interactions in the gap gene system of Drosophila melanogaster.

Abstract

Genetic studies have revealed that segment determination in Drosophila melanogaster is based on hierarchical regulatory interactions among maternal coordinate and zygotic segmentation genes. The gap gene system constitutes the most upstream zygotic layer of this regulatory hierarchy, responsible for the initial interpretation of positional information encoded by maternal gradients. We present a detailed analysis of regulatory interactions involved in gap gene regulation based on gap gene circuits, which are mathematical gene network models used to infer regulatory interactions from quantitative gene expression data. Our models reproduce gap gene expression at high accuracy and temporal resolution. Regulatory interactions found in gap gene circuits provide consistent and sufficient mechanisms for gap gene expression, which largely agree with mechanisms previously inferred from qualitative studies of mutant gene expression patterns. Our models predict activation of Kr by Cad and clarify several other regulatory interactions. Our analysis suggests a central role for repressive feedback loops between complementary gap genes. We observe that repressive interactions among overlapping gap genes show anteroposterior asymmetry with posterior dominance. Finally, our models suggest a correlation between timing of gap domain boundary formation and regulatory contributions from the terminal maternal system.

Full Text

The Full Text of this article is available as a PDF (605K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Finkelstein R, Perrimon N. The orthodenticle gene is regulated by bicoid and torso and specifies Drosophila head development. Nature. 1990 Aug 2;346(6283):485–488. [PubMed]
  • Foe VE, Alberts BM. Studies of nuclear and cytoplasmic behaviour during the five mitotic cycles that precede gastrulation in Drosophila embryogenesis. J Cell Sci. 1983 May;61:31–70. [PubMed]
  • Frasch M, Levine M. Complementary patterns of even-skipped and fushi tarazu expression involve their differential regulation by a common set of segmentation genes in Drosophila. Genes Dev. 1987 Nov;1(9):981–995. [PubMed]
  • Gaul U, Jäckle H. Pole region-dependent repression of the Drosophila gap gene Krüppel by maternal gene products. Cell. 1987 Nov 20;51(4):549–555. [PubMed]
  • Gaul U, Jäckle H. 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. 1989 Nov;107(3):651–662. [PubMed]
  • Goodwin BC, Kauffman SA. Spatial harmonics and pattern specification in early Drosophila development. Part I. Bifurcation sequences and gene expression. J Theor Biol. 1990 Jun 7;144(3):303–319. [PubMed]
  • Grossniklaus U, Cadigan KM, Gehring WJ. Three maternal coordinate systems cooperate in the patterning of the Drosophila head. Development. 1994 Nov;120(11):3155–3171. [PubMed]
  • Harding K, Levine M. Gap genes define the limits of antennapedia and bithorax gene expression during early development in Drosophila. EMBO J. 1988 Jan;7(1):205–214. [PMC free article] [PubMed]
  • Hoch M, Schröder C, Seifert E, Jäckle H. cis-acting control elements for Krüppel expression in the Drosophila embryo. EMBO J. 1990 Aug;9(8):2587–2595. [PMC free article] [PubMed]
  • Hoch M, Seifert E, Jäckle H. Gene expression mediated by cis-acting sequences of the Krüppel gene in response to the Drosophila morphogens bicoid and hunchback. EMBO J. 1991 Aug;10(8):2267–2278. [PMC free article] [PubMed]
  • Hoch M, Gerwin N, Taubert H, Jäckle H. Competition for overlapping sites in the regulatory region of the Drosophila gene Krüppel. Science. 1992 Apr 3;256(5053):94–97. [PubMed]
  • Aizenberg Igor, Myasnikova Ekaterina, Samsonova Maria, Reinitz John. Temporal classification of Drosophila segmentation gene expression patterns by the multi-valued neural recognition method. Math Biosci. 2002 Mar;176(1):145–159. [PubMed]
  • Howard K. The blastoderm prepattern. Semin Cell Biol. 1990 Jun;1(3):161–172. [PubMed]
  • Hülskamp M, Pfeifle C, Tautz D. A morphogenetic gradient of hunchback protein organizes the expression of the gap genes Krüppel and knirps in the early Drosophila embryo. Nature. 1990 Aug 9;346(6284):577–580. [PubMed]
  • Brönner G, Jäckle H. Control and function of terminal gap gene activity in the posterior pole region of the Drosophila embryo. Mech Dev. 1991 Nov;35(3):205–211. [PubMed]
  • Hülskamp M, Lukowitz W, Beermann A, Glaser G, Tautz D. Differential regulation of target genes by different alleles of the segmentation gene hunchback in Drosophila. Genetics. 1994 Sep;138(1):125–134. [PMC free article] [PubMed]
  • Burstein Z. A network model of developmental gene hierarchy. J Theor Biol. 1995 May 7;174(1):1–11. [PubMed]
  • Hunding A, Kauffman SA, Goodwin BC. Drosophila segmentation: supercomputer simulation of prepattern hierarchy. J Theor Biol. 1990 Aug 9;145(3):369–384. [PubMed]
  • Capovilla M, Eldon ED, Pirrotta V. The giant gene of Drosophila encodes a b-ZIP DNA-binding protein that regulates the expression of other segmentation gap genes. Development. 1992 Jan;114(1):99–112. [PubMed]
  • Casanova J. Pattern formation under the control of the terminal system in the Drosophila embryo. Development. 1990 Oct;110(2):621–628. [PubMed]
  • Jaeger Johannes, Surkova Svetlana, Blagov Maxim, Janssens Hilde, Kosman David, Kozlov Konstantin N, Manu, Myasnikova Ekaterina, Vanario-Alonso Carlos E, Samsonova Maria, et al. Dynamic control of positional information in the early Drosophila embryo. Nature. 2004 Jul 15;430(6997):368–371. [PubMed]
  • Clyde Dorothy E, Corado Maria S G, Wu Xuelin, Paré Adam, Papatsenko Dmitri, Small Stephen. A self-organizing system of repressor gradients establishes segmental complexity in Drosophila. Nature. 2003 Dec 18;426(6968):849–853. [PubMed]
  • Knipple DC, Seifert E, Rosenberg UB, Preiss A, Jäckle H. Spatial and temporal patterns of Krüppel gene expression in early Drosophila embryos. Nature. 1985 Sep 5;317(6032):40–44. [PubMed]
  • Kosman D, Small S. Concentration-dependent patterning by an ectopic expression domain of the Drosophila gap gene knirps. Development. 1997 Apr;124(7):1343–1354. [PubMed]
  • Driever W, Nüsslein-Volhard C. The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo. Nature. 1989 Jan 12;337(6203):138–143. [PubMed]
  • Driever W, Thoma G, Nüsslein-Volhard C. Determination of spatial domains of zygotic gene expression in the Drosophila embryo by the affinity of binding sites for the bicoid morphogen. Nature. 1989 Aug 3;340(6232):363–367. [PubMed]
  • Kraut R, Levine M. Mutually repressive interactions between the gap genes giant and Krüppel define middle body regions of the Drosophila embryo. Development. 1991 Feb;111(2):611–621. [PubMed]
  • Eldon ED, Pirrotta V. Interactions of the Drosophila gap gene giant with maternal and zygotic pattern-forming genes. Development. 1991 Feb;111(2):367–378. [PubMed]
  • Kumar Sudhir, Jayaraman Karthik, Panchanathan Sethuraman, Gurunathan Rajalakshmi, Marti-Subirana Ana, Newfeld Stuart J. BEST: a novel computational approach for comparing gene expression patterns from early stages of Drosophila melanogaster development. Genetics. 2002 Dec;162(4):2037–2047. [PMC free article] [PubMed]
  • Rivera-Pomar R, Lu X, Perrimon N, Taubert H, Jäckle H. Activation of posterior gap gene expression in the Drosophila blastoderm. Nature. 1995 Jul 20;376(6537):253–256. [PubMed]
  • Rothe M, Nauber U, Jäckle H. Three hormone receptor-like Drosophila genes encode an identical DNA-binding finger. EMBO J. 1989 Oct;8(10):3087–3094. [PMC free article] [PubMed]
  • Merrill PT, Sweeton D, Wieschaus E. Requirements for autosomal gene activity during precellular stages of Drosophila melanogaster. Development. 1988 Nov;104(3):495–509. [PubMed]
  • Rothe M, Pehl M, Taubert H, Jäckle H. Loss of gene function through rapid mitotic cycles in the Drosophila embryo. Nature. 1992 Sep 10;359(6391):156–159. [PubMed]
  • Mjolsness E, Sharp DH, Reinitz J. A connectionist model of development. J Theor Biol. 1991 Oct 21;152(4):429–453. [PubMed]
  • Rothe M, Wimmer EA, Pankratz MJ, González-Gaitán M, Jäckle H. Identical transacting factor requirement for knirps and knirps-related Gene expression in the anterior but not in the posterior region of the Drosophila embryo. Mech Dev. 1994 Jun;46(3):169–181. [PubMed]
  • Mlodzik M, Gibson G, Gehring WJ. Effects of ectopic expression of caudal during Drosophila development. Development. 1990 Jun;109(2):271–277. [PubMed]
  • Schröder C, Tautz D, Seifert E, Jäckle H. Differential regulation of the two transcripts from the Drosophila gap segmentation gene hunchback. EMBO J. 1988 Sep;7(9):2881–2887. [PMC free article] [PubMed]
  • Mohler J, Eldon ED, Pirrotta V. A novel spatial transcription pattern associated with the segmentation gene, giant, of Drosophila. EMBO J. 1989 May;8(5):1539–1548. [PMC free article] [PubMed]
  • Schulz C, Tautz D. Autonomous concentration-dependent activation and repression of Krüppel by hunchback in the Drosophila embryo. Development. 1994 Oct;120(10):3043–3049. [PubMed]
  • Myasnikova E, Samsonova A, Kozlov K, Samsonova M, Reinitz J. Registration of the expression patterns of Drosophila segmentation genes by two independent methods. Bioinformatics. 2001 Jan;17(1):3–12. [PubMed]
  • Sharp DH, Reinitz J. Prediction of mutant expression patterns using gene circuits. Biosystems. 1998 Jun-Jul;47(1-2):79–90. [PubMed]
  • Shermoen AW, O'Farrell PH. Progression of the cell cycle through mitosis leads to abortion of nascent transcripts. Cell. 1991 Oct 18;67(2):303–310. [PMC free article] [PubMed]
  • Simcox AA, Sang JH. When does determination occur in Drosophila embryos? Dev Biol. 1983 May;97(1):212–221. [PubMed]
  • Nagorcka BN. A pattern formation mechanism to control spatial organization in the embryo of Drosophila melanogaster. J Theor Biol. 1988 Jun 7;132(3):277–306. [PubMed]
  • Simpson-Brose M, Treisman J, Desplan C. Synergy between the hunchback and bicoid morphogens is required for anterior patterning in Drosophila. Cell. 1994 Sep 9;78(5):855–865. [PubMed]
  • Nauber U, Pankratz MJ, Kienlin A, Seifert E, Klemm U, Jäckle H. Abdominal segmentation of the Drosophila embryo requires a hormone receptor-like protein encoded by the gap gene knirps. Nature. 1988 Dec 1;336(6198):489–492. [PubMed]
  • Small S, Blair A, Levine M. Regulation of two pair-rule stripes by a single enhancer in the Drosophila embryo. Dev Biol. 1996 May 1;175(2):314–324. [PubMed]
  • Steingrímsson E, Pignoni F, Liaw GJ, Lengyel JA. Dual role of the Drosophila pattern gene tailless in embryonic termini. Science. 1991 Oct 18;254(5030):418–421. [PubMed]
  • Nüsslein-Volhard C, Wieschaus E. Mutations affecting segment number and polarity in Drosophila. Nature. 1980 Oct 30;287(5785):795–801. [PubMed]
  • Struhl G, Johnston P, Lawrence PA. Control of Drosophila body pattern by the hunchback morphogen gradient. Cell. 1992 Apr 17;69(2):237–249. [PubMed]
  • Pankratz MJ, Hoch M, Seifert E, Jäckle H. Krüppel requirement for knirps enhancement reflects overlapping gap gene activities in the Drosophila embryo. Nature. 1989 Sep 28;341(6240):337–340. [PubMed]
  • Tautz D. Regulation of the Drosophila segmentation gene hunchback by two maternal morphogenetic centres. Nature. 1988 Mar 17;332(6161):281–284. [PubMed]
  • Pankratz MJ, Busch M, Hoch M, Seifert E, Jäckle H. Spatial control of the gap gene knirps in the Drosophila embryo by posterior morphogen system. Science. 1992 Feb 21;255(5047):986–989. [PubMed]
  • Tautz D, Sommer RJ. Evolution of segmentation genes in insects. Trends Genet. 1995 Jan;11(1):23–27. [PubMed]
  • Warrior R, Levine M. Dose-dependent regulation of pair-rule stripes by gap proteins and the initiation of segment polarity. Development. 1990 Nov;110(3):759–767. [PubMed]
  • Reinitz J, Levine M. Control of the initiation of homeotic gene expression by the gap genes giant and tailless in Drosophila. Dev Biol. 1990 Jul;140(1):57–72. [PubMed]
  • Weigel D, Jürgens G, Klingler M, Jäckle H. Two gap genes mediate maternal terminal pattern information in Drosophila. Science. 1990 Apr 27;248(4954):495–498. [PubMed]
  • Reinitz J, Sharp DH. Mechanism of eve stripe formation. Mech Dev. 1995 Jan;49(1-2):133–158. [PubMed]
  • Wu X, Vasisht V, Kosman D, Reinitz J, Small S. Thoracic patterning by the Drosophila gap gene hunchback. Dev Biol. 2001 Sep 1;237(1):79–92. [PubMed]
  • Reinitz J, Mjolsness E, Sharp DH. Model for cooperative control of positional information in Drosophila by bicoid and maternal hunchback. J Exp Zool. 1995 Jan 1;271(1):47–56. [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...