1. An mRNA located internally at the anterior end (encoding a transcription factor, named Bicoid).

  2. An mRNA located internally at the posterior end (encoding an inhibitor of the translation of the mRNA for a transcription factor, named Nanos).

  3. An external protein anchored to the egg shell at both ends of the egg (involved in the production of a ligand of a receptor tyrosine kinase in the egg-cell plasma membrane).

  4. An external protein also anchored to the egg shell but at the prospective ventral side (involved in the production of a signal ligand of the Toll receptor in the egg-cell plasma membrane).

To exemplify the steps of use of those gene products, only one of the dimensions, the anteroposterior, will be described. The two mRNAs are initially at opposite ends of the egg. They are translated after fertilization, and the encoded proteins diffuse from the ends to form opposing gradients reaching to the middle of the egg. These proteins will act in concert to generate a gradient, high at the anterior end and low at the posterior end, of another transcription factor. The nuclear number increases rapidly in the uncleaved cytoplasm. The graded transcription factors, called members of the “coordinate class” or “egg-polarity class” of gene products, activate at least eight gap genes in nuclei along the egg’s length at different positions, each position unique in terms of the local quantity of transcription factors of the coordinate class. (The terms “coordinate,” “egg polarity,” and “gap” also derive from mutant phenotypes.) The encoded gap proteins, which are all transcription factors themselves, accumulate in a pattern of eight broad and partially overlapping stripes along the egg’s length. The proliferating nuclei are not yet separated by cell membranes—that comes later. These proteins in turn activate at least eight pair-rule genes, all of which also encode transcription factors. Complex cis-regulatory regions of the various pair-rule genes define their expression responses to the spatially distributed gap proteins. The pair-rule proteins then activate at least 12 segment-polarity genes, some of which encode transcription factors and some of which encode secreted protein signals. The pair-rule and gap proteins together also activate eight homeobox (Hox) genes to be expressed in broad stripes, as discussed in the next section. Thus, the early steps of development involve cascades of transcription factors distributed in space according to the initial gradients of a few agents and to the expression rules contained in the complex cis-regulatory regions of genes for yet other transcription factors. These key steps are accomplished in the first 3 hours of development, mostly before cell membranes are formed and gastrulation begins, although the final elaboration of the segment-polarity and Hox genes occurs after cells form.

Once the segment-polarity genes and Hox genes are activated, they maintain their expression in cells by an auto-activating circuitry, in some cases by the encoded transcription factor activating expression of its own gene. The coordi-



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