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Abstract
Drosophila has recently become a powerful model system to understand the mecha-
nisms of temporal patterning of neural progenitors called neuroblasts (NBs). Two differ-
ent temporal sequences of transcription factors (TFs) have been found to be sequentially
expressed in NBs of two different systems: the Hunchback, Krüppel, Pdm1/Pdm2, Castor,
and Grainyhead sequence in the Drosophila ventral nerve cord; and the Homothorax,
Klumpfuss, Eyeless, Sloppy-paired, Dichaete, and Tailless sequence that patterns medulla
NBs. In addition, the intermediate neural progenitors of type II NB lineages are patterned
by a different sequence: Dichaete, Grainyhead, and Eyeless. These three examples sug-
gest that temporal patterning of neural precursors by sequences of TFs is a common
theme to generate neural diversity. Cross-regulations, including negative feedback reg-
ulation and positive feedforward regulation among the temporal factors, can facilitate
the progression of the sequence. However, there are many remaining questions to
understand the mechanism of temporal transitions. The temporal sequence progression
is intimately linked to the progressive restriction of NB competence, and eventually
determines the end of neurogenesis. Temporal identity has to be integrated with spatial
identity information, as well as with the Notch-dependent binary fate choices, in order to
generate specific neuron fates.
1. INTRODUCTION
One fundamental question in developmental neurobiology is to under-
stand how to generate the remarkable diversity of neurons and glia present in
adult brains, from a small number of seemingly homogenous neural stem cells
in the embryo. Spatial patterning of neural stemcells that is achieved by various
morphogens and their signaling cascades contributes to the generation of neu-
ral diversity ( Bhat, 1999a; Dessaud, McMahon, & Briscoe, 2008 ). Further-
more, single neural stem cells can generate different neural types in a
stereotyped order: This is achieved by temporal patterning of neural stem cells.
Extensive studies in the vertebrate central nervous system (CNS), especially
cerebral cortex and retina, have revealed that birth order correlates with dis-
tinct neuronal/glial identity (reviewed in Jacob, Maurange, & Gould, 2008;
Livesey & Cepko, 2001; Molyneaux, Arlotta, Menezes, & Macklis, 2007;
Okano & Temple, 2009; Pearson & Doe, 2004 ). Although both extrinsic
and intrinsic factors are required for the correct specification of tem-
poral identify, isolated neural stem cells cultured in vitro can recapitulate the
sequential generation of different neuron types, thus underscoring a cell-
intrinsic temporal control of stem cells ( Gaspard et al., 2008; Naka,
Nakamura, Shimazaki, & Okano, 2008; Shen et al., 2006 ).
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