21–13 The mouse HoxA3 and HoxD3 genes are paralogs that occupy equivalent positions in their respective Hox gene clusters and share roughly 50% identity in their pro-tein-coding sequences. Mice with defects in HoxA3 have deficiencies in pharyngeal tissues, whereas mice with defects in HoxD3 have deficiencies in the axial skeleton, suggesting quite different functions for the paralogs. Thus, it came as a surprise when it was found that replacing a defective HoxD3 gene with the normal HoxA3 gene corrected the deficiency, as did the reciprocal experiment of replacing a mutant HoxA3 gene with a normal HoxD3 gene. Neither transplaced gene, however, could supply its normal function; that is, a normal HoxA3 gene at the HoxD3 locus could not correct the deficiency caused by a mutant HoxA3 gene at the HoxA3 locus. The same was true for the HoxD3 gene. If the HoxA3 and HoxD3 genes are equivalent, how do you suppose they can play such distinct roles in development? Why do you suppose they cannot perform their normal function in a new location?
21–14 The segmentation of somites in vertebrate embryos is thought to depend on oscillations in the expression of the Hes7 gene. Mathematical modeling explains these oscillations in terms of the delays in production of the unstable Hes7 protein, which acts as a transcription regulator to shut off its own expression. Once Hes7 decays, with a half-life of about 20 minutes, its transcription resumes. To test this model, you decide to reduce the total delay by removing one, two, or all three of the introns from the Hes7 gene in mice. Why do you expect that intron removal would reduce the delay? What would you predict would happen to the oscillation time, and somite formation, if the model were correct?
21–15 The oscillatory clock that drives somite formation in vertebrates involves three essential components Her7 (an unstable repressor of its own synthesis), Delta (a transmembrane signaling molecule), and Notch (a trans-membrane receptor for Delta). Notch is bound by Delta on neighboring cells, activating the Notch signaling pathway, which then activates Her7 transcription. Normally, this system works flawlessly to create sharply defined somites (Figure Q21–2A). In the absence of Delta, however, only the first five somites form normally, and the rest are poorly defined (Figure Q21–2B). If a pulse of Delta is supplied later, somite formation returns to normal in the regions where Delta was present (Figure Q21–2C). A diagram of the connections between the components of the clock and how they interact in adjacent cells is shown in Figure Q21–2D. In the absence of Delta, why do the cells become unsynchronized? What is it about the presence of Delta that keeps adjacent cells oscillating in synchrony?
21–16 The extracellular protein factor Decapentaplegic (Dpp) is critical for proper wing development in Drosophila (Figure Q21–3A). It is normally expressed in a narrow stripe in the middle of the wing, along the anterior–posterior boundary. Flies that are defective for Dpp form stunted “wings” (Figure Q21–3B). If an additional copy of the gene is placed under control of a promoter that is active in the anterior part of the wing, or in the posterior
Figure Q21–2 Somite formation in zebrafish embryos (problem 21–15).