Key Points
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Asymmetric cell division is an important mechanism for generating cell diversity in the Drosophila nervous system. Insights from this system could also help us to understand the role of asymmetric cell division in the vertebrate nervous system. Most neurons in Drosophila are generated from neural precursors — neuroblasts in the central nervous system and sensory organ precursors (SOPs) in the peripheral nervous system — as a result of stereotyped sequences of asymmetric cell divisions.
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Neuroblasts divide to give rise to an apical neuroblast and a basal ganglion mother cell (GMC). Cell-fate determinants, such as Numb and Prospero, become localized to the basal cortex of the dividing neuroblast so that they are segregated into the GMC after division. SOPs undergo several rounds of asymmetric cell division to produce all the cells of a sensory organ, and Numb and Prospero are also important in this process.
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The orientation of division is controlled by apical–basal polarity in neuroblasts, but by planar polarity in SOPs. Many of the genes involved in the control of the orientation of division have been identified, including bazooka, which is important in both neuroblasts and SOPs.
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The polar segregation of determinants such as Numb is tightly coupled to the orientation of the spindle. In inscuteable loss-of-function mutants, the neuroblast spindle fails to align with the polarity cues. Evidence from budding yeast indicates that the cells may use a 'search-and-capture' mechanism to align the spindle, in which the spindle see-saws to and fro until microtubules find binding sites in the cell cortex.
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The localization of cell-fate determinants to a crescent at one pole of the dividing cell seems to be a multistep process. In the case of Pon (Partner of Numb), the initial stage is independent of actomyosin, but later stages are not. Genes that are important for this process include lgl and dlg.
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Crescent formation and spindle orientation occur at specified stages in the cell cycle. Disruption of the cell cycle prevents the correct segregation of determinants into crescents and orientation of the spindle.
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Many questions remain to be answered about the molecular mechanisms that are involved in asymmetric cell division. Recent advances have improved our understanding of these processes in Drosophila, and further work should clarify whether, and how, asymmetric cell division contributes to the development of the vertebrate nervous system.
Abstract
Asymmetric cell division is a fundamental means of generating cell-fate diversity. Our understanding of the molecular mechanisms of asymmetric cell division in the Drosophila nervous system has advanced greatly in recent years, and insights gained from it might help to unravel the role of asymmetric cell division in the development of vertebrate nervous systems.
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Acknowledgements
We thank F. Roegiers and S. Barbel for help with the figures. We are both investigators of the Howard Hughes Medical Institute.
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Glossary
- HOMEODOMAIN-CONTAINING PROTEINS
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Proteins with a 60-amino-acid DNA-binding domain that comprises three α-helices.
- EGF REPEAT
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A motif with ∼50 amino acids, including six cysteine residues and a mainly β-sheet structure, found in growth factors and extracellular matrix proteins.
- PDZ DOMAIN
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A peptide-binding domain that is important for the organization of membrane proteins, particularly at cell–cell junctions, including synapses. They can bind to the carboxyl termini of proteins, or can form dimers with other PDZ domains. PDZ domains are named after the proteins in which these sequence motifs were originally identified (PSD95, Discs -large, zona occludens 1).
- NOTUM
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The dorsal or top surface of the thorax.
- IMAGINAL DISC
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A single-cell layer epithelial structure of the Drosophila larva that gives rise to wings, legs and other appendages.
- RNA-MEDIATED INTERFERENCE
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A process by which an introduced double-stranded RNA specifically silences the expression of genes through degradation of their cognate mRNA.
- ADHERENS JUNCTIONS
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Cell–cell or cell–matrix adhesive junctions that are linked to cytoskeletal microfilaments.
- WD40 REPEAT
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A repeat of ∼40 amino acids with a characteristic central tryptophan–aspartate motif.
- ZINC FINGER
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A protein module in which cysteine or cysteine–histidine residues coordinate a zinc ion. Zinc fingers are often used in DNA recognition and in protein–protein interactions.
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Jan, YN., Jan, L. Asymmetric cell division in the Drosophila nrevous system. Nat Rev Neurosci 2, 772–779 (2001). https://doi.org/10.1038/35097516
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DOI: https://doi.org/10.1038/35097516
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