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

Abstract

Temporal patterning of neural progenitors is one of the core mechanisms generating neuronal diversity in the central nervous system. Here, we show that in the tips of the outer proliferation center (tOPC) of the developing Drosophila optic lobes, a unique temporal series of transcription factors not only governs the sequential production of distinct neuronal subtypes, but also controls the mode of progenitor division as well as the selective apoptosis of NotchOFF or NotchON neurons during binary cell fate decisions. Within a single lineage, intermediate precursors initially do not divide and generate only one neuron; subsequently, precursors divide but their NotchON progeny systematically die through Reaper activity whereas later, their NotchOFF progeny die through Hid activity. These mechanisms dictate how the tOPC produces neurons for three different optic ganglia. We conclude that temporal patterning generates neuronal diversity by specifying both the identity and survival/death of each unique neuronal subtype.

Neural stem cell progeny regulate stem cell death in a Notch and Hox dependent manner

“…In contrast, when abdA is knocked down (l, wor4abdAi) Dl expression is largely confined to the NB (j′-l′) Dl expression with brightness adjusted to highlight this difference. (m, m′) The glia cells form a more elaborate network around the NBs in the abdominal neuromeres (green repo4mCD8GFP, red Dpn) of the developing CNS in flies and mammals, 27,28,[42][43][44] and is involved in the non-autonomous regulation of cell survival by hedgehog signaling in the developing eye. 29 We find that the N pathway is required for NB death in the embryo, in contrast to previous data showing that N is not involved in pNB death later in development.…”

So many pieces, one puzzle: cell type specification and visual circuitry in flies and mice

“…However, this has now been addressed systematically in several new studies, leading to a description of how cellular diversity in the fly visual system is generated (Li et al 2013a;Suzuki et al 2013;Bertet et al 2014; for review, see Li et al 2013b). The mechanisms of neuronal specification in the medulla neuropil share surprising similarities with that of the fly embryonic ventral nerve cord, where each neural stem cell (called a neuroblast [NB]) expresses sequentially a series of transcription factors ( Fig.…”

sequoia controls the type I>0 daughter proliferation switch in the developing Drosophila nervous system

“…The generation of neurons and glia by each progenitor can occur by three basic modes: as directly differentiating neurons; via an intermediate daughter that divides once to generate two neurons/glia; or via a daughter that divides multiple times to generate several neurons/glia (Kriegstein et al, 2006;Fish et al, 2008;Franco and Muller, 2013). These three basic proliferation modes have been described in many animal species, and in Drosophila they are referred to as type 0, type I and type II, respectively (Bello et al, 2008;Boone and Doe, 2008;Bowman et al, 2008;Baumgardt et al, 2014;Bertet et al, 2014). The control of alternate daughter proliferation is of profound importance because it can act to expand the number of neurons/glia generated at a certain temporal stage in a developing lineage (Ulvklo et al, 2012).…”