Facilitator Questions #3 Wieschaus

Bicoid provides dipteran (fly) embryos with positional information such that target genes are expressed at the correct position. Outside the dipterans there is no Bicoid. How are those embryos provided with positional information? Do you expect to find a gene like bicoid (eg a morphogen)? Alternatively, how else could positional information be provided? Do you think there could be a gene like bicoid that controls early development in humans? What feature of human development would argue for or against the existence of such a gene?

The expression patterns of zygotic genes (hunchback, etc) scale with egg length. How could scaling be achieved, and how is it actually achieved? For the characteristic length of the Bicoid concentration profile (l) to scale with egg length, what do you predict for either the diffusion coefficient D or the life-time of Bicoid in different eggs?

Diffusion in eggs of different sizes is roughly similar and therefore (within the framework of the simple model) for the length constant l to scale, the life-time of Bicoid has to increase with the size of the eggs. On the other hand, for the gradient to be at steady-state, the life-time has to be much smaller than the interval between fertilization and the time at which the gradient is utilized. Use the numbers for D, l and life-time given in Wieschaus’ presentation and in the literature and show the limits to scaling.

How could the life-time of Bicoid change from species to species? What do you know about degradation of proteins in general? Are there motifs (sequences) that render a protein stable/unstable? How can you identify these motifs? Could you engineer (and how) a Bicoid with a different lifetime? Assume you had succeeded in obtaining a short-lived and a long-lived version of Bicoid. What do you predict the resulting gradient would look like? What would the gap gene expression pattern look like?

If the lifetime of Bicoid was solely determined by a degradation motif, what would you expect by expressing Bicoid from a big species in a small one? What was actually found? How do you explain the finding?