shuttle craft


DEVELOPMENTAL BIOLOGY

Embryonic

During cycles of syncytial nuclear division in early embryogenesis, a maternally derived source of Stc protein exhibits a dynamic cell cycle-dependent nuclear distribution pattern, which is eventually lost once the synchronous division cycles end at blastoderm cellularization. After fertilization, Stc protein derived from maternal transcripts are evenly distributed throughout the embryo. By the ninth syncytial nuclear cleavage cycle, Stc protein specifically localizes within the nuclei. At the completion of syncytial division cycles, at blastoderm cellulariztion, Stc protein is no longer localized in interphase nuclei, and its intracellular distribution is not localized. Zygotic expression of Stc protein is detected in stage 13 to 17 embryos where it is prominent in the nuclei of subsets of cells in the CNS. Expression is restricted to the nuclei of repeated clusters of cells located in each neuromere along the length of the ventral cord and to distinct groups of cells located within the brain lobes. Hence, its limited zygotic distribution suggests a possible role for Stc protein in the development of the CNS (Stroumbakis, 1996).

Adult

STC transcripts are expressed throughout oogenesis in all follicle cells and nurse cells and are transferred by the latter into the oocyte at stage 10b, where they are maintained after fertilization within the embryo. Stc protein is first detected in the nuclei of follicle cells present in the posterior half of the germarium. Throughout oogenesis, STC protein is abundantly present in the nuclei of anterior and posterior terminal follicle cells. This nuclear expression first covers a number of cells within these spatial domains but is eventually refined by stage 10 of oogenesis to two cells at the anterior (i.e. a subset of migrating border cells) and two at the posterior end of the oocyte. By stage 12 of oogenesis, all follicle cells accumulate Stc protein in their nuclei. Stc protein is also observed in the cytoplasm of nurse cells and the oocyte. In addition, nurse cell nuclei contain Stc protein concentrated in two or three distinct spherical structures of unknown origin. Though Stc protein is abundant in ovaries, studies of germ-line mutants shows that it is not required for the completion of oogenesis (Stroumbakis, 1998).

Effects of Mutation or Deletion

shuttle craft mutants die at the end of embryogenesis, when they appear to be incapable of coordinating the typical peristaltic contraction waves normally required for embryos to hatch into feeding first instar larvae. Preliminary evidence indicates that the resulting lethality of this behavioral defect is accompanied by subtle morphological abnormalities in the central nervous system, where in wild-type embryos, Stc protein is normally localized in the nuclei of repeated cell clusters within each neuromere and brain lobe (Stroumbakis, 1996). shuttle craft is expressed zygotically in the embryonic central nervous system (CNS) where it is required to maintain the proper morphology of motoneuronal axon nerve routes following their migration from the ventral cord. A prominent maternal source of Stc protein is also present throughout both oogenesis and embryogenesis. To determine whether this maternal component is required in the ovary and/or embryo, the Drosophila autosomal dominant female sterile technique was employed to generate germ-line clones that lack the stc maternal function. A maternally derived source of STC protein is required during embryogenesis but not oogenesis. In contrast to the zygotic phenotype, the primary defect in embryos derived from stc germ-line clones affects segmentation by causing disruptions and deletions in distinct thoracic (T1-T3) and abdominal (A4-A8) segments. These localized defects are responsible for additional phenotypes observed later in development that include gaps in the ventral nerve cord and deletions of denticle belts in the cuticle. An additional phenotype occurring in all other neuromeric segments consists of the misguided migration of motoneuronal axons as they project out of the ventral nerve cord. Thus, the stc zygotic function is required later in development and cannot correct the segmentation and subsequent CNS abnormalities associated with loss of its earlier acting maternally derived activity (Tolias, 1998).

Variation in longevity in natural populations is attributable to the segregation of multiple interacting loci, whose effects are sensitive to the environment. Although there has been considerable recent progress towards understanding the environmental factors and genetic pathways that regulate lifespan, little is known about the genes causing naturally occurring variation in longevity. Deficiency complementation mapping was used to map two closely linked quantitative trait loci (QTL) causing female-specific variation in longevity between the Oregon (Ore) and 2b strains of Drosophila melanogaster to 35B9-C3 and 35C3 on the second chromosome. The 35B9-C3 QTL encompasses a 50-kb region including four genes, for one of which, shuttle craft (stc), mutations have been generated. The 35C3 QTL localizes to a 200-kb interval with 15 genes, including three genes for which mutations exist [reduced (rd), guftagu (gft) and ms(2)35Ci]. Quantitative complementation tests to mutations at these four positional candidate genes were performed; ms(2)35Ci and stc are novel candidate quantitative trait genes affecting variation in Drosophila longevity. Complementation tests with stc alleles reveal sex- and allele-specific failure to complement, and complementation effects are dependent on the genetic background, indicating considerable epistasis for lifespan. In addition, a homozygous viable stc allele has a sex-specific effect on lifespan. stc encodes an RNA polymerase II transcription factor, and is an attractive candidate gene for the regulation of longevity and variation in longevity, because it is required for motoneuron development and is expressed throughout development. Quantitative genetic analysis of naturally occurring variants with subtle effects on lifespan can identify novel candidate genes and pathways important in the regulation of longevity (Pasyukova, 2004).

Embryonic expression of shuttle craft, a Drosophila gene involved in neuron development, is associated with adult lifespan

Despite the progress in aging research that highlights the role of the nervous system in longevity, whether genes that control development and consequently structure of the nervous system affect lifespan is unclear. This study demonstrates that a mutation in shuttle craft, a gene involved in the nervous system development, increased the lifespan of unmated females and decreased the lifespan of mated females, without affecting males. Precise reversions of the mutation lead to the restoration of the lifespan specific to control females. In mutant unmated females, increased lifespan was associated with elevated locomotion at older ages, indicating slowed aging. In mutant mated females, reproduction was decreased compared to controls, indicating a lack of tradeoff between this trait and lifespan. No differences in shuttle craft transcription were observed between whole bodies, ovaries, and brains of mutant and control females of different ages, either unmated or mated. The amount of shuttle craft transcript appeared to be substantially decreased in mutant embryos. These results demonstrated that a gene that regulates development of the nervous system might also influence longevity, and thus expanded the spectrum of genes involved in lifespan control. It is hypothesized that this 'carry-over' effect might be the result of transcription regulation in embryos (Roshina, 2014: PubMed).


REFERENCES

Pasyukova, E. G., Roshina, N. V. and Mackay, T. F. (2004). Shuttle craft: a candidate quantitative trait gene for Drosophila lifespan. Aging Cell. 3(5): 297-307. 15379853

Roshina, N. V., Symonenko, A. V., Krementsova, A. V., Trostnikov, M. V. and Pasyukova, E. G. (2014). Embryonic expression of shuttle craft, a Drosophila gene involved in neuron development, is associated with adult lifespan. Aging (Albany NY) 6(12): 1076-93. PubMed ID: 25567608

Song, Z., et al. (1994). A novel cysteine-rich sequence-specific DNA-binding protein interacts with the conserved X-box motif of the human major patibility complex class II genes via a repeated Cys-His domain and functions as a transcriptional repressor. J. Exp. Med. 180(5): 1763-74. PubMed ID: 7964459

Stroumbakis, N. D., Li, Z. and Tolias, P. P. (1996). A homolog of human transcription factor NF-X1 encoded by the Drosophila shuttle craft gene is required in the embryonic central nervous system. Mol. Cell. Biol. 16(1): 192-201. PubMed ID: 8524296

Tolias, P. P. and Stroumbakis, N. D. (1998). The Drosophila zygotic lethal gene shuttle craft is required maternally for proper embryonic development. Dev. Genes Evol. 208(5): 274-82. PubMed ID: 9683743


shuttle craft: Biological Overview | Evolutionary Homologs | Developmental Biology | Effects of Mutation

date revised: 25 March 2005

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