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Drosophila Anillin is unequally required during asymmetric cell divisions of the PNS
Södertörn University, School of Life Sciences. Karolinska Institutet.
Södertörn University, School of Life Sciences.
2008 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 369, no 2, 407-413 p.Article in journal (Refereed) Published
Abstract [en]

During Drosophila embryogenesis, timely and orderly asymmetric cell divisions ensure the correct number of each cell type that make up the sensory organs of the larval PNS. We report a role of scraps, Drosophila Anillin, during these divisions. Anillin, a constitutive member of the contractile ring is essential for cytokinesis in Drosophila and vertebrates. During embryogenesis we find that zygotically transcribed scraps is required specifically for the unequal cell divisions, those in which cytokinesis occurs in an "off-centred" manner, of the pIIb and pIIIb neuronal precursor cells, but not the equal cell divisions of the lineage related precursor cells. Complementation and genetic rescue studies demonstrate this effect results from zygotic scraps and leads to polyploidy, ectopic mitosis, and loss of the neuronal precursor daughter cells. The net result of which is the formation of incomplete sense organs and embryonic lethality.

Place, publisher, year, edition, pages
2008. Vol. 369, no 2, 407-413 p.
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:sh:diva-14151DOI: 10.1016/j.bbrc.2008.02.060ISI: 000254676900023PubMedID: 18295597Scopus ID: 2-s2.0-40949150197OAI: oai:DiVA.org:sh-14151DiVA: diva2:467026
Available from: 2011-12-18 Created: 2011-12-16 Last updated: 2016-12-29Bibliographically approved
In thesis
1. A screen for mutations affecting PNS development in Drosophila identifies the trim gene, dappled
Open this publication in new window or tab >>A screen for mutations affecting PNS development in Drosophila identifies the trim gene, dappled
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The peripheral nervous system of Drosophila melanogaster contains a variety of sense organs, ranging from the relatively simple four celled bristle organ to the more complex compound eye. The development of each organ type is well described, providing a useful backdrop for functional studies of genes acting in one or more of the many processes involved in organogenesis. We have used the bristle organ to screen for genes affecting PNS development. Two of the candidates recovered via this approach, string (stg, Drosophila cdc25, the universal regulator of the G2 to M phase mitotic transition), and dappled (dpld, a poorly described gene implicated in tumor suppression) were selected for further study. Examination of stg mis-expression phenotypes in the adult bristle organ revealed cell fate transformations corresponding to the generation of two pIIa structural precursor cells at the expense of a neural precursor cell. This transformation most reasonably resulted from an abnormally short G2 arrest, indicating that the time spent in the G2 phase is crucial to correct cell fate determination. dpld is a member of the Tripartite Motif (TRIM) superfamily, members of which are involved in diverse biological processes e.g. proliferation, apoptosis and immune response. dpld belongs to a subgroup of NHL domain containing TRIM proteins, that are known to be involved in tumor suppression. Phylogenetic analysis placed dpld in the lin-41 sub-clade of the TRIM superfamily. A combination of insilico, genetic and cell culture assay approaches showed dpld to be susceptible to miRNA regulation. As homologous genes are also miRNA regulated this regulatory mechanism may be conserved throughout this sub-clade, between vertebrates and invertebrates. Pre-existing loss of function dpld alleles were characterized, however, subsequent complementation studies revealed that characteristic aspects of the described dpld phenotype, in fact mapped outside the dpld locus, and were caused by mutations of nearby genes. The tumor-causing locus was mapped to the Cytb5 gene (mutated in both pre-existing dpld alleles), while the embryonic lethality and PNS phenotype was mapped to the scraps locus. scraps encodes for Drosophila Anillin, known to be required during cytokinesis. We provide the first characterization of scraps null alleles and detail a biased requirement for scraps within neural precursor cells of the embryonic PNS. A novel loss of function dpld allele was recovered. This mutation is lethal, however it does not have an associated tumor phenotype. This finding, together with our complementation study indicates that the existing classification of dpld as a tumor suppressor is inaccurate. Subsequent studies detail dpld requirements in the developing fly retina. There, dpld mutation resulted in excessive proliferation, while conversely, mis-expression caused a reduction. Additionally, and perhaps consequently, cell differentiation was affected. Thus, regulation of proliferation by NHL-TRIM genes seems a conserved feature. We additionally identified a novel Drosophila TRIM gene of the same class as dpld, which we have dubbed another bbox affiliate (abba), bringing the number of NHL containing TRIM genes in Drosophila to four.

Place, publisher, year, edition, pages
Stockholm: Karolinska institutet, 2008. 68 p.
National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-31553 (URN)978-91-7357-589-8 (ISBN)
Public defence
2008-05-30, MB416, Moas Båge, Huddinge, 13:00
Opponent
Supervisors
Available from: 2016-12-29 Created: 2016-12-29 Last updated: 2016-12-29Bibliographically approved

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