Neuroblast entry into quiescence is regulated intrinsically by the combined action of spatial Hox proteins and temporal identity factors

Abstract

Neural stem cell quiescence is an important feature in invertebrate and mammalian central nervous system development, yet little is known about the mechanisms regulating entry into quiescence, maintenance of cell fate during quiescence, and exit from quiescence. Drosophila neural stem cells (called neuroblasts) provide an excellent model system for investigating these issues. Drosophila neuroblasts enter quiescence at the end of embryogenesis and resume proliferation during larval stages; however, no single neuroblast lineage has been traced from embryo into larval stages. Here, we establish a model neuroblast lineage, NB3-3, which allows us to reproducibly observe lineage development from neuroblast formation in the embryo, through quiescence, to the resumption of proliferation in larval stages. Using this new model lineage, we show a continuous sequence of temporal changes in the neuroblast, defined by known and novel temporal identity factors, running from embryonic through larval stages, and that quiescence suspends but does not alter the order of neuroblast temporal gene expression. We further show that neuroblast entry into quiescence is regulated intrinsically by two independent controls: spatial control by the Hox proteins Antp and Abd-A, and temporal control by previously identified temporal transcription factors and the transcription co-factor Nab.

A genetic cascade involving klumpfuss, nab and castor specifies the abdominal leucokinergic neurons in the Drosophila CNS

“…Third, ABLKs are the unique cells expressing Lk in the ventral ganglion. However, we have not observed downregulation of cas in nab mutants, and the same has been reported in the better characterized lineages of NB3-3 and NB5-6 (Baumgardt et al, 2009;Tsuji et al, 2008); together, these results indicate that the molecular relationship between Cas and Nab requires a more complex interpretation than a linear genetic cascade.…”

“…Recently, part of the underlying genetic mechanism controlling such temporal transitions in progenitor competence has been revealed (Brody and Odenwald, 2000;Cleary and Doe, 2006;Grosskortenhaus et al, 2005;Grosskortenhaus et al, 2006;Isshiki et al, 2001;Kambadur et al, 1998;Novotny et al, 2002;Pearson and Doe, 2003;Tran and Doe, 2008;Tsuji et al, 2008). These studies have identified the temporal identity genes, which are sequentially expressed in the NB and act to specify temporal windows in which the different GMCs are produced.…”

“…The different colors represent the patterns of expression of the various NBs. In A-H and N the separate channels are shown at the bottom of each figure. and Doe, 2003;Tran and Doe, 2008;Tsuji et al, 2008). The transcription factors Hunchback (Hb), Krüppel (Kr), Nubbin (Nub) and Pdm2 (henceforth Pdm), Castor (Cas) and Grainyhead (Grh) are transiently expressed in a temporal sequence in NBs, and their expression is correlated with the production of distinct cell types.…”

Atlas-builder software and the eNeuro atlas: resources for developmental biology and neuroscience

“…pCC, EW1-EW3, Apterous+ neurons and Eve+ lateral interneurons (Doe et al, 1988;Higashijima et al, 1996;Park et al, 2004;Thomas et al, 1984;Tsuji et al, 2008). The eNeuro atlas expands the number of identified interneurons to 958, each of which has been assigned a unique name, and each of which is described by quantitative information on cell body position, size and frequency of appearance, as well as its Gal4 line expression profile (supplementary material Data File S8).…”

G2-phase arrest prevents bristle progenitor self-renewal and synchronizes cell divisions with cell fate differentiation

“…Developmental G2 phase arrest mediated by inhibitory phosphorylation of the Cdk1 mitotic regulator is an important mechanism for coordinating these processes in neural precursor cells O'Farrell, 1989, 1990). Precisely how G2 phase arrest contributes to neural development remains unclear (Tsuji et al, 2008).…”