Identification of Drosophila type II neuroblast lineages containing transit amplifying ganglion mother cells

Abstract

Mammalian neural stem cells generate transit amplifying progenitors that expand the neuronal population, but these type of progenitors have not been studied in Drosophila. The Drosophila larval brain contains approximately 100 neural stem cells (neuroblasts) per brain lobe, which are thought to bud off smaller ganglion mother cells (GMCs) that each produce two post-mitotic neurons. Here, we use molecular markers and clonal analysis to identify a novel neuroblast cell lineage containing "transit amplifying GMCs" (TA-GMCs). TA-GMCs differ from canonical GMCs in several ways: each TA-GMC has nuclear Deadpan, cytoplasmic Prospero, forms Prospero crescents at mitosis, and generates up to 10 neurons; canonical GMCs lack Deadpan, have nuclear Prospero, lack Prospero crescents at mitosis, and generate two neurons. We conclude that there are at least two types of neuroblast lineages: a Type I lineage where GMCs generate two neurons, and a type II lineage where TA-GMCs have longer lineages. Type II lineages allow more neurons to be produced faster than Type I lineages, which may be advantageous in a rapidly developing organism like Drosophila.

Opportunities lost and gained: Changes in progenitor competence during nervous system development

“…2c). 13,14,15 In this section, we will discuss how (a) embryonic type I neuroblasts lose competence to respond to early temporal transcription factors due to changes in subnuclear gene position, (b) larval type I neuroblasts lose competence to respond to oncogenic mutations, (c) larval INPs lose competence to respond to Notch signaling, (d) larval type II neuroblasts use Trithorax to maintain competence to generate INPs, and (e) sensory neuron progenitors change competence to respond to Notch signaling.…”

“…13,14,15,32 Type II neuroblasts divide asymmetrically to generate a series of INPs that produce an average of 10 neurons each, whereas larval type I neuroblasts make GMCs that only produce a pair of neurons. 13,14,15 How do type II neuroblasts generate INPs rather than GMCs?…”

“…13,14,15,32 Type II neuroblasts divide asymmetrically to generate a series of INPs that produce an average of 10 neurons each, whereas larval type I neuroblasts make GMCs that only produce a pair of neurons. 13,14,15 How do type II neuroblasts generate INPs rather than GMCs? Recent work demonstrated that type II neuroblasts require the Buttonhead (Btd) transcription factor to maintain INP production, and that Trithorax (member of the SET1/MLL histone methyltransferase complex) is required to maintain the btd locus in a permissive chromatin state, allowing its expression in type II neuroblasts.…”

Insights into brain development and disease from neurogenetic analyses in Drosophila melanogaster

“…All of these neurons derive from a restricted set of neural stem cell-like progenitors, called neuroblasts, which originate in the neuroectoderm of the early embryo (Urbach and Technau 2004;Doe 2008;Knoblich 2008;Egger et al 2008;Reichert 2011;Homem and Knoblich 2012 Technau et al 2006). In this manner positional information is imparted to the cells of the neuroectoderm in the form of a combinatorial gene expression code (figure 1).…”

“…These large primary progenitor cells are highly proliferative and typically undergo multiple rounds of asymmetric cell divisions, in which they self-renew and at the same time generate a smaller daughter cell called a GMC which divides once to produce two postmitotic neural cells (Doe 2008;Knoblich 2008;Egger et al 2008;Reichert 2011). Due to its delamination from the neuroectoderm, each neuroblast largely retains the gene expression pattern of the neuroectodermal region from which it derives.…”