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Open Access Highly Accessed Research article

A mosaic genetic screen for novel mutations affecting Drosophila neuroblast divisions

Cathy Slack13, W Gregory Somers23, Rita Sousa-Nunes23, William Chia23* and Paul M Overton3*

Author Affiliations

1 Department of Biology, University College London, Gower Street, London WC1E 6BT, UK (current address)

2 Temasek Lifesciences Laboratory, The National University of Singapore, 117604, Singapore

3 MRC Centre for Developmental Neurobiology, King's College London, UK

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BMC Genetics 2006, 7:33  doi:10.1186/1471-2156-7-33

Published: 2 June 2006

Abstract

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 (

    M
osaic
    A
nalysis with a
    R
epressible
    C
ell
    M
arker) 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.