(Top) Nuclear Bicoid protein gradient in a fixed transgenic Drosophila embryo carrying a Bicoid–GFP fusion gene. Image courtesy of Julien O. Dubuis and Thomas Gregor. (Bottom) Bicoid–GFP protein (green) and FISH-labeled bicoid mRNA (red) in the anterior tip of a fixed transgenic Drosophila embryo. Both embryos are oriented with the anterior pole at left. Image courtesy of Shawn C. Little and Thomas Gregor (see Little et al. for methods[1]).
Bicoid mRNA is actively localized to the anterior of the fruit fly egg during oogenesis[6] along microtubules[7] by the motor protein dynein,[8] and retained there through association with cortical actin.[9] Translation of bicoid is regulated by its 3′ UTR and begins after egg deposition. Diffusion and convection within the syncytium produce an exponential gradient of Bicoid protein[2][10] within roughly one hour, after which Bicoid nuclear concentrations remain approximately constant through cellularization.[11] An alternative model proposes the formation of a bicoid mRNA gradient in the embryo along cortical microtubules which then serves as template for translation of the Bicoid protein to form the Bicoid protein gradient.[12][13][14] Bicoid protein represses the translation of caudal mRNA and enhances the transcription of anterior gap genes including hunchback, orthodenticle, and buttonhead.
Structure and function
PyMOL rendering of Bicoid homeodomain bound to its consensus site
Bicoid is one of the few proteins which uses its homeodomain to bind both DNA and RNA targets to regulate their transcription and translation, respectively. The nucleic acid-binding homeodomain of Bicoid has been solved by NMR.[15] Bicoid contains an arginine-rich motif (part of the helix shown axially in this image) that is similar to the one found in the HIV protein REV and is essential for its nucleic acid binding.[16]
Bicoid mutant produces no head
Bicoid protein gradient formation is one of the earliest steps in fruit fly embryo A-P patterning. The proper spatial expression of downstream genes relies on the robustness of this gradient to common variations between embryos, including in the number of maternally-deposited bicoid mRNAs and in egg size. Comparative phylogenetic[17] and experimental evolution[18] studies suggest an inherent mechanism for robust generation of a scaled Bicoid protein gradient. Mechanisms that have been proposed to effect this scaling include non-linear degradation of Bicoid,[19] nuclear retention as a size-dependent regulator of Bicoid protein's effective diffusion coefficient,[10][20] and scaling of cytoplasmic streaming.[10]
^ abDriever W, Nüsslein-Volhard C (July 1988). "The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner". Cell. 54 (1): 95–104. doi:10.1016/0092-8674(88)90183-3. PMID3383245. S2CID18830552.
^St Johnston D, Driever W, Berleth T, Richstein S, Nusslein-Volhard C (1989). "Multiple steps in the localization of bicoid RNA to the anterior pole of the Drosophila oocyte". Development. 107: 13–19. doi:10.1242/dev.107.Supplement.13. PMID2483989.
^Frigerio G, Burri M, Bopp D, Baumgartner S, Noll M (December 1986). "Structure of the segmentation gene paired and the Drosophila PRD gene set as part of a gene network". Cell. 47 (5): 735–746. doi:10.1016/0092-8674(86)90516-7. PMID2877746. S2CID9658875.
^Baird-Titus JM, Clark-Baldwin K, Dave V, Caperelli CA, Ma J, Rance M (March 2006). "The solution structure of the native K50 Bicoid homeodomain bound to the consensus TAATCC DNA-binding site". Journal of Molecular Biology. 356 (5): 1137–1151. doi:10.1016/j.jmb.2005.12.007. PMID16406070.
