response, but perturbation of the redox status of the cell and oxidative stress are often, if not always, involved. As in other pathways, the apoptotic pathway engages in cross-talk, for example, with the nuclear factor-kappaB (NF-kB) and INF and FAS pathways. A recent report demonstrates that heat shock (43°C) can rapidly activate the stress-activated protein kinase pathways mediated by c-JUN terminal kinase (JNK) and p38 (Wilson et al. 1999).

As noted for the drug-metabolizing enzymes discussed in Chapter 5, these molecular-stress and checkpoint pathways deserve attention as elements of the organism’s defense against physical and chemical interventions. It remains to be learned whether polymorphisms of defense components exist in humans, compromising their responses to environmental agents. The extent to which the germ line, gametes, and early embryos operate these molecular-stress and checkpoint pathways is also poorly understood.

Developmental Differences

Although Drosophila and mouse development share more similarities than anyone thought 15 years ago, significant differences do exist. Mice share more aspects of development with other chordates (the chordate phylum includes vertebrates, cephalochordates, and urochordates) than they do with Drosophila, and they share still more aspects with other mammals. There appear to be “nested similarities” of development (i.e., the more recent the common ancestor of two groups, the more shared features of their development). Regarding HOX genes, for example, chordates have four more kinds of genes (HOX 10-13) than do arthropods. These differ slightly in sequence from the others and are located at the 5′ end of each cluster. They are expressed in the postanal tail, which is a chordate structure not shared by arthropods, and also in the developing vertebrate limb. Still, the difference between chordates and arthropods is a modification of a shared feature, namely, the use of HOX genes to divide the anteroposterior dimension of the animal into nonequivalent spatial compartments.

Chordates, but not arthropods, share the development of a dorsal hollow nerve cord, a notochord, and a segmentally arranged pharyngo-branchial apparatus, in addition to a postanal tail. They also share a kind of development involving a centralized “organizer” group of cells, the Spemann organizer, which releases inducers important in the placement, orientation, and scaling of later development by surrounding cells. The inducers secreted by the organizer have now been identified. Several inducers are secreted protein antagonists of the TGFβ and WNT signals and are used by surrounding cells to maintain their ventral posterior paths of development. The inducer antagonists disinhibit and hence release the inherent capacity of the surrounding cells to undertake dorsal anterior kinds of development (e.g., to form the neural tube rather than epidermis) (Harland and Gerhart 1997; Smith and Schoenwolf 1998; Weinstein and Hemmati-Brivanlou 1999). Few researchers would have guessed a few years ago



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