Establishment of the Drosophila Embryonic Body Plan

We have previously discussed the establishment of the anterior-posterior and dorsal-ventral axes in the Drosophila oocyte. We shall now turn our attention to the utilization of that pre-pattern in generation of the embryonic body plan. We shall also examine some of the parallels between body plan formation in Drosophila, Caenorhabditis elegans and mammals. Initial development in Drosophila is unique in many regards because the early embryo develops as a syncytium. Thus, it can utilize mechanisms that are not relevant to cellular embryos. For example, morphogen gradients are established in the syncytium to create asymmetry. The longitudinal axis is established by the distribution of bicoid and nanos mRNA; bicoid mRNA is localized at the anterior end, whereas nanos is localized at the posterior end. Diffusion of Bicoid and Nanos proteins from the opposite poles produces a gradient of Hunchback, which is a transcription factor. Hunchback, in turn, generates a transcription factor cascade that specifies anterior-posterior pattern.

Bicoid and Nanos have quite different effects on production of Hunchback. Bicoid is a transcriptional regulator that activates transcription of the hunchback gene in anterior nuclei, whereas nanos represses translation of oognenic hunchback mRNA in the posterior region of the embryo via negative regulatory elements in the hunchback 3' UTR, called nanos-response elements (NREs; Wharton and Struhl, 1991). The net result is an anterior-posterior gradient of Hunchback protein (Fig. 1, Wharton and Struhl, 1991). The proposed interaction between Nanos and hunchback mRNA is poorly understood, and there is no direct evidence that Nanos interacts directly with the NREs on hunchback. In a recent study of factors that do bind to the NREs, Murata and Wharton (1995) have described two NRE-binding proteins. One of these proteins is encoded by pumilio, a gene that is essential for abdominal segmentation. This paper will be discussed in a student seminar.

In addition to its role as a transcription factor, Bicoid protein is involved in repressing translation of caudal mRNA, which is another actor in axis formation. The normal gradient of Caudal protein is low in the anterior to high in the posterior. In the absence of Bicoid activity, that gradient is disrupted, and high amounts of Caudal accumulate in the anterior end. Bicoid protein appears to influence translation of the caudal mRNA by binding to its 3' UTR (Dubnau, 1995). The anti-parallel gradients that affect establishment of the axis are illustrated in Figure 4 (Wickens et al., 1996).

nanos (nos) itself is subject to translational regulation that is reminiscent of the requirement for localization of osk mRNA for its translation (Rongo et al., 1995). Embryos from mothers mutant for the genes that mediate posterior localization of nos develop abdominal defects that are typical of embryos produced by nos mutant mothers. This result suggests that the embryos are deficient in Nos protein, a possibility that has been confirmed by immunoblotting (Fig. 1b, Gavis and Lehmann, 1994). Northern blots reveal that nos mRNA is present in normal amounts in these embryos (Fig. 1a). This suggests that the failure to localize the RNA prevents its translation. Thus, in the wild-type, localization overcomes this translational inhibition. It has been demonstrated that the nos 3' UTR governs the localization of this transcript (Gavis and Lehmann, 1992). Does the 3' UTR also mediate translational regulation? To examine this possibility, Gavis and Lehmann (1994) deliberately mislocalized nos mRNA to the anterior end of embryos by replacing the nos 3' UTR with that of bcd. As a results, nos transcripts were localized to the anterior end of embryos, where they were translated. Then, they added a nos 3' UTR to the nos-bcd hybrid. Transcripts from this gene were localized to the anterior end of the embryos, but they were not translated there (Fig. 4, Gavis and Lehmann, 1994). Thus, localization is not sufficient; localization must be to the posterior end. This result has been interpreted to mean that translation inhibitory factors will bind to the nos 3' UTR to prevent translation unless it is localized to the posterior end of the embryo, where this inhibition is relieved.

A similar mechanism to the nanos/hunchback system may operate in early C. elegans development. This mechanism involves translational regulation of glp-1, which encodes a transmembrane protein (GLP-1) involved in early signaling events that are necessary for development of the pharynx.

Gametogenesis

From Sperm and Egg to Embryo

Genetic Regulation of Development

Organizing the Multicellular Embryo

Generating Cell Diversity

The Foundations of Developmental Biology

Learning Resources

Research Resources

 

Developmental Biology Tutorial

The Developmental Biology Journal Club

Digging Deeper:

Murata, Y. and R.P. Wharton. 1995. Binding of Pumilio to maternal hunchback mRNA is required for posterior patterning in Drosophila embryos. Cell 80: 747-756.

Another excellent review of patterning of the Drosophila embryo has been written by Bloom (Bloom, T. Patterning the Drosophila embryo. 1996. Current Biology 6: 6-8.).


References

Dubnau, J. 1995. Homeodomain RNA regulation. Ph.D. thesis, Columbia University, New York, N.Y. (cited in Wickens et al., 1996).

Evans, T.C., S.L. Crittendon, V. Kodoyianni and J. Kimble. 1994. Translational control of maternal glp-1 mRNA establishes an asymmetry in the C. elegans embryo. Cell 77: 183-194.

Gavis, E.R. and R. Lehmann. 1992. Localization of nanos RNA controls embryonic polarity. Cell 71: 301-313.

Gavis, E.R. and R. Lehmann. 1994. Translational regulation of nanos by RNA localization. Nature 369: 315-318.

Sulston, J.E., E. Schierenberg, J.G. White and J.N. Thomson. 1983. The embryonic cell lineage of the nematode Caenorhabditis elegans. Develop. Biol. 100: 64-119.

Wharton, R.P. and G. Struhl. 1991. RNA regulatory elements mediate control of Drosophila body pattern by the posterior morphogen nanos. Cell 67: 955-967.

Wickens, M., J. Kimble and S. Strickland. 1996. Translational control of developmental decisions. In J.W.B. Hershey, M.B. Matthews and N. Sonenberg (Eds.),Translational Control, Cold Spring Harbor Laboratory Press, Plainview, N.Y., pp 411-450

Browder, L.W. 1996, 1997. Establishment of the Drosophila Embryonic Body Plan. In L.W. Browder (Ed.), Developmental Biology, <http://www.ucalgary.ca/~browder>.

Copyright © 1996 Leon W. Browder. This material may be reproduced for educational purposes only provided credit is given to the original source.

August 7, 1997