§ Dept. of Genetics, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel, # Dept. of Biology, University of Michigan, Ann Arbor, MI 48109, @ Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030.,
The gutfeeling (guf) gene was uncovered in a genetic screen aimed at identifying genes that are required for proper development of the embryonic peripheral nervous system. Mutations in guf cause defects in growth cone guidance and fasciculation and loss of expression of several neuronal markers in the embryonic peripheral and central nervous system. Detailed phenotypic analyses indicate that guf is required for terminal differentiation of neuronal cells. Mutations in guf also affect the development of muscles in the embryo. In the absence of guf activity, myoblasts are formed properly, but myoblast fusion and further differentiation of muscle fibers is severly impaired. The guf gene 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 biosynthetic pathway through its binding to, and inhibition of, ornithine decarboxylase, the first enzyme in the pathway. The elaborate regulation of ODC activity in mammals still lacks a defined developmental role and very little is known about the involvement of polyamines in cellular differentiation. GUF is the first antizyme-like protein identified in invertebrates. I will discuss its possible developmental roles in light of this homology.