Further Development 2.3: Transcription Factor Gradients Specify Fates from Head to Tail

Specifying Identity: Mechanisms of Developmental Patterning

As we will detail in Chapter 9, the anteriormost portion of the Drosophila embryo produces a transcription factor called Bicoid, with a concentration of both mRNA and protein that is highest in the anterior region of the egg and declines toward the posterior (FIGURE 1A,B; Gregor et al. 2007; Sample and Shvartsman 2010; Little et al. 2011). The posteriormost portion of the egg forms a posterior-to-anterior gradient of the transcription factor Caudal. Thus, the long axis of the Drosophila egg is spanned by opposing gradients: Bicoid from the anterior and Caudal from the posterior (FIGURE 1C). Bicoid and Caudal are considered morphogens because they occur in a concentration gradient and are capable of regulating different genes at different threshold concentrations.

Nuclei in regions containing high amounts of Bicoid and little Caudal are instructed to activate the genes that produce the head. In regions with little or no Bicoid but plenty of Caudal, the activated genes form abdominal/tail structures, while regions with concentrations in between the two extremes result in thorax fates (Nüsslein-Volhard et al. 1987). Thus, when the syncytial nuclei are eventually incorporated into cells, these cells will have their general fate specified. Afterward, the specific fate of each cell will become determined both autonomously (from transcription factors acquired after cellularization) and conditionally (from interactions between the cell and its neighbors).

**FIGURE 1**Morphogen gradients during syncytial specification in *Drosophila* *melanogaster*. (A) Expression of Bicoid protein in the early embryo is shown in green. (B) Quantification of Bicoid distribution along the anterior-posterior axis demonstrates that concentrations are highest anteriorly and diminish posteriorly. (C) Anterior-posterior specification originates from morphogen gradients in the egg cytoplasm, specifically of the transcription factors Bicoid and Caudal. The concentrations and ratios of these two proteins distinguish each position along the axis from any other position. When nuclear division occurs, the amounts of each morphogen differentially activate transcription of the various nuclear genes that specify the segment identities of the larval and the adult fly. (As we will see in Chapter 9, the Caudal gradient is itself constructed by interactions between constituents of the egg cytoplasm.) (B from C. Sample and S. Y. Shvartsman. 2010. *Proc Natl Acad Sci USA* 107: 10092.)

Developing Questions

If a mechanism of opposing concentration gradients of Bicoid and Caudal determines specification of the anteriorposterior axis in Drosophila melanogaster, could this same mechanism work in a fly embryo that is larger or has different proportions per body segment, or would it need some modification? How precise is the actual gradient, and how precise does it actually have to be to set a nucleus/cell on a lineage-specific path of maturation?

Literature Cited

Gregor, T., D. W. Tank, E. F. Wieschaus and W. Bialek. 2007. Probing the limits to positional information. Cell 130: 153–164.
PubMed Link

Little, S. C., G. Tkačik, T. B. Kneeland, E. F. Wieschaus and T. Gregor. 2011. The formation of the Bicoid morphogen gradient requires protein movement from anteriorly localized mRNA. PLOS Biol. 9: e1000596.
PubMed Link

Nüsslein-Volhard, C., H. G. Fröhnhofer and R. Lehmann. 1987. Determination of anterioposterior polarity in Drosophila. Science 238: 1675–1681.
PubMed Link

Sample, C. and S. Y. Shvartsman. 2010. Multiscale modeling of diffusion in the early Drosophila embryo. Proc. Natl. Acad. Sci. USA 107: 10092–10096.
PubMed Link

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