Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe

Abstract

BackgroundThe choice of a stem cell to divide symmetrically or asymmetrically has profound consequences for development and disease. Unregulated symmetric division promotes tumor formation, whereas inappropriate asymmetric division affects organ morphogenesis. Despite its importance, little is known about how spindle positioning is regulated. In some tissues cell fate appears to dictate the type of cell division, whereas in other tissues it is thought that stochastic variation in spindle position dictates subsequent sibling cell fate.ResultsHere we investigate the relationship between neural progenitor identity and spindle positioning in the Drosophila optic lobe. We use molecular markers and live imaging to show that there are two populations of progenitors in the optic lobe: symmetrically dividing neuroepithelial cells and asymmetrically dividing neuroblasts. We use genetically marked single cell clones to show that neuroepithelial cells give rise to neuroblasts. To determine if a change in spindle orientation can trigger a neuroepithelial to neuroblast transition, we force neuroepithelial cells to divide along their apical/basal axis by misexpressing Inscuteable. We find that this does not induce neuroblasts, nor does it promote premature neuronal differentiation.ConclusionWe show that symmetrically dividing neuroepithelial cells give rise to asymmetrically dividing neuroblasts in the optic lobe, and that regulation of spindle orientation and division symmetry is a consequence of cell type specification, rather than a mechanism for generating cell type diversity.

Temporal Patterning of Neuroblasts Controls Notch-Mediated Cell Survival through Regulation of Hid or Reaper

“…It derives from a single-layered crescent-shaped neuroepithelium in the larval brain called the o uter p roliferation c enter (OPC). The OPC is progressively converted into progenitors (called neuroblasts) by a wave of expression of the pro-neural gene lethal of scute that sweeps from the edge toward the center of the crescent over time (Egger et al, 2007; Egger et al, 2010; Ngo et al, 2010; Yasugi et al, 2010)(Fig. S1A).…”

Insights into neural stem cell biology from flies

“…In Drosophila, proliferative symmetric divisions are found in the developing optic lobes (White & Kankel 1978;Hofbauer & Campos-Ortega 1990;Ceron et al 2001;Egger et al 2007). However, most Drosophila neuroblasts divide asymmetrically by self-renewing and budding-off smaller GMCs.…”

A Regulatory Transcriptional Loop Controls Proliferation and Differentiation in Drosophila Neural Stem Cells

“…The AS-C is composed of four transcription factors called Achaete (Ac), Scute (Sc), Lethal of Scute (L(1)sc), and Asense (Ase) [40]. While Ac is not expressed in the optic lobe, three of four AS-C proteins show specific expression [8],[9]. Sc is expressed in the NE cells and NBs, L(1)sc is transiently expressed in the transition zone between NE cells and NBs, and Ase is expressed in NBs and GMCs in the developing medulla (Figures 2A–2A’’’ show expression of Ase) [8], [9].…”

“…While Ac is not expressed in the optic lobe, three of four AS-C proteins show specific expression [8],[9]. Sc is expressed in the NE cells and NBs, L(1)sc is transiently expressed in the transition zone between NE cells and NBs, and Ase is expressed in NBs and GMCs in the developing medulla (Figures 2A–2A’’’ show expression of Ase) [8], [9]. To test which of the AS-C genes might act with Da during cell fate determination in medulla NBs, we induced clones of several deletion lines that uncover the AS-C region (Figures 2B–2E, clones in the optic lobe were induced by NP7340-Gal4 and UAS-flp [36]).…”