A mosaic genetic screen for novel mutations affecting Drosophila neuroblast divisions.

Publisher: BioMed Central Country of Publication: England NLM ID: 100966978 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2156 (Electronic) Linking ISSN: 14712156 NLM ISO Abbreviation: BMC Genet Subsets: MEDLINE

Original Publication: London : BioMed Central, [2000-

Germ-Line Mutation* ; Mosaicism*; Drosophila/*genetics ; Ganglia, Invertebrate/*embryology; Animals ; Brain/cytology ; Brain/embryology ; Cell Cycle Proteins/genetics ; Drosophila/embryology ; Drosophila Proteins/genetics ; Female ; Ganglia, Invertebrate/cytology ; Genes, Lethal ; Genetic Testing ; Larva/genetics ; Larva/growth & development ; Male ; Phenotype

Background: The asymmetric segregation of determinants during cell division is a fundamental mechanism for generating cell fate diversity during development. In Drosophila, neural precursors (neuroblasts) divide in a stem cell-like manner generating a larger apical neuroblast and a smaller basal ganglion mother cell. The cell fate determinant Prospero and its adapter protein Miranda are asymmetrically localized to the basal cortex of the dividing neuroblast and segregated into the GMC upon cytokinesis. Previous screens to identify components of the asymmetric division machinery have concentrated on embryonic phenotypes. However, such screens are reaching saturation and are limited in that the maternal contribution of many genes can mask the effects of zygotic loss of function, and other approaches will be necessary to identify further genes involved in neuroblast asymmetric division.
Results: We have performed a genetic screen in the third instar larval brain using the basal localization of Miranda as a marker for neuroblast asymmetry. In addition to the examination of pupal lethal mutations, we have employed the MARCM (Mosaic Analysis with a Repressible Cell Marker) system to generate postembryonic clones of mutations with an early lethal phase. We have screened a total of 2,300 mutagenized chromosomes and isolated alleles affecting cell fate, the localization of basal determinants or the orientation of the mitotic spindle. We have also identified a number of complementation groups exhibiting defects in cell cycle progression and cytokinesis, including both novel genes and new alleles of known components of these processes.
Conclusion: We have identified four mutations which affect the process of neuroblast asymmetric division. One of these, mapping to the imaginal discs arrested locus, suggests a novel role for the anaphase promoting complex/cyclosome (APC/C) in the targeting of determinants to the basal cortex. The identification and analysis of the remaining mutations will further advance our understanding of the process of asymmetric cell division. We have also isolated a number of mutations affecting cell division which will complement the functional genomics approaches to this process being employed by other laboratories. Taken together, these results demonstrate the value of mosaic screens in the identification of genes involved in neuroblast division.

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United Kingdom WT_ Wellcome Trust

0 (Cell Cycle Proteins)
0 (Drosophila Proteins)
0 (Mira protein, Drosophila)

Date Created: 20060606 Date Completed: 20060816 Latest Revision: 20230408

20230410

PMC1523195

10.1186/1471-2156-7-33

16749923