A conserved nuclear receptor, Tailless, is required for efficient proliferation and prolonged maintenance of mushroom body progenitors in the Drosophila brain

Abstract

The intrinsic neurons of mushroom bodies (MBs), centers of olfactory learning in the Drosophila brain, are generated by a specific set of neuroblasts (Nbs) that are born in the embryonic stage and exhibit uninterrupted proliferation till the end of the pupal stage. Whereas MB provides a unique model to study proliferation of neural progenitors, the underlying mechanism that controls persistent activity of MB-Nbs is poorly understood. Here we show that Tailless (TLL), a conserved orphan nuclear receptor, is required for optimum proliferation activity and prolonged maintenance of MB-Nbs and ganglion mother cells (GMCs). Mutations of tll progressively impair cell cycle in MB-Nbs and cause premature loss of MB-Nbs in the early pupal stage. TLL is also expressed in MB-GMCs to prevent apoptosis and promote cell cycling. In addition, we show that ectopic expression of tll leads to brain tumors, in which Prospero, a key regulator of progenitor proliferation and differentiation, is suppressed whereas localization of molecular components involved in asymmetric Nb division is unaffected. These results as a whole uncover a distinct regulatory mechanism of self-renewal and differentiation of the MB progenitors that is different from the mechanisms found in other progenitors.

Transcriptomes of lineage-specific Drosophila neuroblasts profiled via genetic targeting and robotic sorting

“…6F). Consistent with the known requirement of Tll for MB neurogenesis (Kurusu et al, 2009), the SoxN-positive MBs showed reduced neuron numbers and aberrant morphologies (data not shown). This exemplifies the importance of lineage-specific expression or repression of various TFs in programming distinct NBs and their production of lineage-characteristic progenies.…”

“…6B′). By contrast, Tll is abundant in the offspring of MB NBs (Kurusu et al, 2009) (Fig. 6C, arrows) and the developing optic lobe (Li et al, 2013), but could not be detected within the AL lineages (Fig.…”

The Orphan Nuclear Receptor TLX/NR2E1 in Neural Stem Cells and Diseases

“…Prospero, which encodes a homeodomain transcription factor associated with the differentiation of ganglion mother cells after asymmetric stem cell division of neuroblasts in the central brain [42,43], is the only target gene that has been found to be directly regulated by Tll in postembryonic stages [44]. In the mouse, multiple genes involved in the development of the CNS and visual system have been identified as Tlx targets, such as Gsh2, Pax2, Pten, p21, p57, S100b, Aqp4, Plce1, Wnt7a, microRNA-9, Bmp4, and GFAP [21,[32][33][34][35][36][37][45][46][47][48][49][50] (Table 1).…”

“…In contrast, in the ganglion mother cells derived from neuroblasts through asymmetric division, a lack of tll expression and elevated prospero expression promote differentiation [42,43]. It has been reported that ectopic expression of tll in ganglion mother cells inhibits apoptosis, promotes cell-cycle progression, and results in tumor formation in the Drosophila brain [44].…”

DrosophilaCORL is required for Smad2-mediated activation of Ecdysone Receptor expression in the mushroom body

“…In the developing brain, at stage 13 CORL first appears in one or two cells within the ventral-most part of the trito-and deutocerebrum, and in small groups of cells in lateral regions of the ocular protocerebrum ( Fig (18) neurons and toy mutants die with visible MB defects (FurukuboTokunaga et al, 2009). The MB is the site of many cognitive functions and receives input from a variety of sources (Truman et al, 1994;Davis, 1996).…”