GUTFEELING, A DROSOPHILA GENE ENCODING AN ANTIZYME-LIKE PROTEIN, IS REQUIRED FOR LATE DIFFERENTIATION OF NEURONS AND MUSCLES

The gutfeeling (guf) gene was uncovered in a genetic screen for genes that are required for proper development of the embryonic peripheral n ervous system. Mutations in guf cause defects in growth cone guidance and fasciculation and loss of expression of several neuronal markers i n the embryonic peripheral and central nervous systems. guf is require d for terminal differentiation of neuronal cells. Mutations in guf als o affect the development of muscles in the embryo. In the absence of g uf activity, myoblasts are formed properly, but myoblast fusion and fu rther differentiation of muscle fibers is severely impaired. The guf g ene was cloned and found to encode a 21-kD protein with a significant sequence similarity to the mammalian ornithine decarboxylase antizyme (OAZ). In mammals, OAZ plays a key regulatory role in the polyamine bi osynthetic pathway through its binding to, and inhibition of, ornithin e decarboxylase (ODC), the first enzyme in the pathway. The elaborate regulation of ODC activity in mammals still lacks a defined developmen tal role and little is known about the involvement of polyamines in ce llular differentiation. GUF is the first antizyme-like protein identif ied in invertebrates. We discuss its possible developmental roles in l ight of this homology.