The Questions of Developmental Biology

Homologous Pathways of Development
One of the most exciting findings of the past decade has been the existence not only of
homologous regulatory genes, but also of homologous signal transduction pathways (Zuckerkandl
1994; Gilbert 1996; Gilbert et al. 1996). Many of those pathways have been mentioned earlier in
this book. They are composed of homologous proteins arranged in a homologous manner. In this
respect, the homology is similar to that of a human forearm and a seal flipper. The parts-the
proteins-are homologous, and the structures they make up-the pathways-are homologous.
Homologous pathways form the basic infrastructure of development. The targets of these
pathways may differ, however, among organisms. For example, the Dorsal-Cactus pathway used
in Drosophila for specifying dorsal-ventral polarity is also used by the mammalian immune
system to activate inflammatory proteins (see Figure 9.38). This does not mean that the
Drosophila blastoderm is homologous to the human macrophage. It merely means that there is a
very ancient pathway that predates the deuterostome-protostome split, and that this pathway can
be used in different systems. The pathways (one in Drosophila, one in humans) are homologous;
the organs they form are not.
Another ancient pathway is the RTK pathway (see Figure 6.14). In Drosophila, the
determination of photoreceptor 7 is accomplished when the Sevenless protein (on the presumptive
photoreceptor 7) binds to the Bride of sevenless (Boss) protein on photoreceptor 8.
This interaction activates the receptor tyrosine kinase of the Sevenless protein to phosphorylate
itself. The Drk protein then binds to these newly phosphorylated tyrosines through its Srchomology-2
(SH2) region and activates the Son of sevenless (SOS) protein. This protein is a
guanosine nucleotide exchanger and exchanges GDP for GTP on the Ras1 G protein.
This activates the G protein, enabling it to transmit its signal to the nucleus through the MAP
kinase cascade (Figure 22.12). This same system has been found to be involved in the
determination of the nematode vulva, the mammalian epidermis, and the Drosophila terminal
segments. The similarity in these systems is so striking that many of the components are
interchangeable between species. The gene for human GRB2 can correct the phenotypic defects
of sem-5-deficient nematodes, and the nematode SEM-5 protein can bind to the phosphorylated
form of the human EGF receptor (Stern et al. 1993). Thus, in the ectoderm of one organism, the
RTK pathway may activate the genes responsible for proliferation.