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Control of neural stem cell self-renewal and differentiation in Drosophila

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Abstract

The neural stem cells of Drosophila, called neuroblasts, have the ability to self-renew and at the same time produce many different types of neurons and glial cells. In the central brain and ventral ganglia, neuroblasts are specified and delaminate from the neuroectoderm during embryonic development under the control of proneural and neurogenic genes. In contrast, in the optic lobes, neuroepithelial cells are transformed into neuroblasts postembryonically by a spatial wave of proneural gene expression. Central brain and ventral nerve cord neuroblasts manifest a short embryonic proliferation period followed by a stage of quiescence and then undergo a prolonged postembryonic proliferation period during which most of the differentiated neurons of the adult CNS are generated. While most neuroblasts belong to a type I class that produces neuronal lineages through non-self-renewing ganglion mother cells, a small subset of type II neuroblasts generates exceptionally large neuronal lineages through self-renewing intermediate progenitor cells that have a transit amplifying function. All neuroblasts in the CNS generate their neural progeny through an asymmetric cell division mode in which the interplay of apical complex and basal complex molecules in the mitotically active progenitor results in the segregation of cell fate determinants into the smaller more differentiated daughter cell. Defects in this molecular control of asymmetric cell division in neuroblasts can result in brain tumor formation. Proliferating neuroblast lineages in the developing CNS utilize transcription factor cascades as a generic mechanism for temporal patterning and birth order-dependent determination of differential neural cell fate. This contributes to the generation of a remarkable diversity of cell types in the developing CNS from a surprisingly small set of neural stem cell-like precursors.

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Abbreviations

aPKC:

Atypical protein kinase C

CNS:

Central nerve system

Gαi:

G protein α i subunit 65A

INP:

Intermediate neural progenitor

Mud:

Mushroom body defect

Par3:

Partitioning defect 3

Par6:

Partitioning defect 6

Pins:

Partner of Inscuteable

Pon:

Partner of Numb

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Acknowledgments

We thank Yanrui Jiang for critical reading of the manuscript. This work was supported by grants from the Swiss National Research Program 63 (4063 L 128006) and the Swiss National Science Foundation (31003A 140607) as well as by grants from the Global Research Laboratory Program (NRF-2009-00424), Brain Research Program (NRF-2009-0081465), and Stem Cell Research Program (NRF-2006-2004289) of the Korean Ministry of Science, ICT, and Future Planning (MSIP).

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  1. KAIST Institute of BioCentury, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, South Korea

    Kyung Hwa Kang

  2. Biozentrum, University of Basel, Klingelbergstrasse 50/70, Basel, CH-4056, Switzerland

    Heinrich Reichert

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Kang, K.H., Reichert, H. Control of neural stem cell self-renewal and differentiation in Drosophila . Cell Tissue Res 359, 33–45 (2015). https://doi.org/10.1007/s00441-014-1914-9

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