Mechanisms of neuronal death during development--insights from chick motoneurons.

During normal development, large numbers of cells undergo a temporally and spatially specific period of programmed cell death (PCD). The study of PCD is an area of intense research in many disciplines, including oncology, immunology and neurobiology. Understanding this process should provide keys to developing therapeutic strategies based on initiating cell death, a desire in cancer therapies, or preventing cell death in neurodegenerative diseases. This somewhat obvious notion pinpoints the purpose of this article. Cell death research blankets many fields contributing to an explosive acquisition of data from many sources. These data however, have not been universally consistent with information relevant to one area, such as mitotically active cancer cells versus that of another area, such as postmitotic neurons. This review article will outline some issues that we currently understand to underlie biochemical and molecular mechanisms mediating neuronal death in the developing CNS. Considering the amount of research currently directed toward understanding the pathways of cell death, we will attempt to identify components that appear to be common in all cell deaths as well as those possibly unique to neuronal death.

Dictyostelium discoideum myoJ: a member of a broadly defined myosin V class or a class XI unconventional myosin?

The simple eukaryote Dictyostelium discoideum contains at least 12 unconventional myosin genes. Here we report the characterization of one of these, myoJ, a gene initially identified through a physical mapping screen. The myoJ gene encodes a high molecular weight myosin, and analysis of the available deduced amino acid sequence reveals that it possesses six IQ motifs and sequences typical of alpha helical coiled coils in the tail region. Therefore, myoJ is predicted to exist as a dimer with up to 12 associated light chains (six per heavy chain). The 7.8 kb myoJ mRNA is expressed all throughout the life cycle of D. discoideum. The myoJ gene has been disrupted and a phenotypic analysis of the mutant cells initiated. Finally, phylogenetic analysis of the head region reveals that myoJ is most similar to two plant myosin genes, Arabidopsis MYA1 and MYA2, that have been alternatively suggested to be either members of the myosin V class or founding members of the myosin XI class.

Molecular genetic analysis of myoF, a new Dictyostelium myosin I gene.

Several new members of the Dictyostelium myosin family have been identified by physical mapping techniques in combination with PCR. Here we describe the initial molecular genetic characterization of one of these, myoF. A 1-kb segment of the myoF gene was obtained by the PCR and used as a specific probe for Northern analysis and as a vehicle for gene-targeting studies. The myoF gene is expressed as a 3.7-kb message, a size consistent with it encoding a myosin I class unconventional myosin, bringing the total of myosin is present in Dictyostelium to six. Analysis of strains in which the myoF gene has been disrupted reveals that loss of the myoF protein does not result in obvious defects either in cellular translocation, or in other readily assayed actin-based processes. The results of our investigation indicate that the myosin I family is quite large in Dictyostelium, and that several members, including myoF, may either be functionally redundant or play roles in as yet undescribed actin-based processes.