On the roles of Notch, Delta, kuzbanian, and inscuteable during the development of Drosophila embryonic neuroblast lineages

Abstract

The generation of cellular diversity in the nervous system involves the mechanism of asymmetric cell division. Besides an array of molecules, including the Par protein cassette, a heterotrimeric G protein signalling complex, Inscuteable plays a major role in controlling asymmetric cell division, which ultimately leads to differential activation of the Notch signalling pathway and correct specification of the two daughter cells. In this context, Notch is required to be active in one sibling and inactive in the other. Here, we investigated the requirement of genes previously known to play key roles in sibling cell fate specification such as members of the Notch signalling pathway, e.g., Notch (N), Delta (Dl), and kuzbanian (kuz) and a crucial regulator of asymmetric cell division, inscuteable (insc) throughout lineage progression of 4 neuroblasts (NB1-1, MP2, NB4-2, and NB7-1). Notch-mediated cell fate specification defects were cell-autonomous and were observed in all neuroblast lineages even in cells born from late ganglion mother cells (GMC) within the lineages. We also show that Dl functions non-autonomously during NB lineage progression and clonal cells do not require Dl from within the clone. This suggests that within a NB lineage Dl is dispensable for sibling cell fate specification. Furthermore, we provide evidence that kuz is involved in sibling cell fate specification in the central nervous system. It is cell-autonomously required in the same postmitotic cells which also depend on Notch function. This indicates that KUZ is required to facilitate a functional Notch signal in the Notch-dependent cell for correct cell fate specification. Finally, we show that three neuroblast lineages (NB1-1, NB4-2, and NB7-1) require insc function for sibling cell fate specification in cells born from early GMCs whereas insc is not required in cells born from later GMCs of the same lineages. Thus, there is differential requirement for insc for cell fate specification depending on the stage of lineage progression of NBs.

Asymmetric Cell Division and Notch Signaling Specify Dopaminergic Neurons in Drosophila

“…Alternatively, Insc is only strictly required in cells born early in the NB lineages hence later born DA neurons within the same clusters are not affected resulting in less than double the size of neurons in these clusters. Differential requirement for insc based on the birth order of cells in NB lineages has been demonstrated in some embryonic NB lineages [49]. Collectively, our data indicates a critical role of the ACD mechanism in fate specification of most DA neurons in Drosophila .…”

“…Notch has been described as an effector of asymmetric cell division and binary sibling cell fate resolution [11], [48], [49]. To investigate the role of Notch signaling in the specification of embryonic DA neurons, we first analyzed TH expression in the ventral midline of Notch 55e11 mutants and found supernumerary TH expressing cells.…”

“…This suggests that Insc may either be partially redundant or may not be required for specification of PM DA neurons. A partial redundancy of Insc has been described for the specification of MP2 cells [56] as well as in late born cells within some NB lineages [49].…”

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.…”

Specification of neuronal subtypes by different levels of Hunchback

“…The Notch signaling pathway plays a role in distinguishing the fates of these two postmitotic cells (fates A and B) (Udolph et al, 2009). To address the role of Notch in the specification of CCAP neurons we examined its expression in mutants of sanpodo (spdo), a gene required for asymmetric cell division (Babaoglan et al, 2009 We examined whether the number of CCAP neurons was altered in Df(3L)H99 embryos and found that an extra CCAP cell appeared in segments SE1-T2, whereas in T3 and the abdominal segments the number was not altered (Fig.…”