Notch Signaling and the Generation of Cell Diversity in Drosophila Neuroblast Lineages

Abstract

Notch is a membrane bound transcription factor and it plays fundamental roles in many cell-cell interaction events usually involving directly neighboring cells relating an extrinsic signal of a sending cell to the nucleus of the receiving cell to modulate gene expression patterns in this cell. Notch regulates cell fate specification, cell proliferation as well as cell death in the contexts of many organs and cell types. Although the mechanisms of signal transduction from the cell surface to the nucleus are relatively simple, it is not fully understood how such a straightforward pathway can result in tremendously complex outcomes at the cellular level. This chapter discusses some of the known roles of Notch during central nervous system development in Drosophila. In the CNS, Notch is a major player in creating cellular diversity on the level of binary cell fates by possibly activating differential gene expression in sibling cells arising through asymmetric cell division. This chapter also raises some questions related to Notch function during neural cell fate specification which have not yet been satisfactorily addressed in the field. Finding answers to these questions may provide further insights into how cell-cell interactions in the nervous system involving Notch control the generation of cellular diversity.

Level of Notch activation determines the effect on growth and stem cell-like features in glioblastoma multiforme neurosphere cultures

“…The involvement of Notch in cell-fate decisions during development of the nervous system was originally outlined through studies in D. melanogaster, and it has been demonstrated that Notch signaling influences the balance between the NSC pool and its differentiated progeny through both lateral inhibition as well as inductive and restrictive cell fate determination. [18][19][20][21][22][23][24][25] The Notch receptors have been associated with cells in neurogenic areas such as the subventricular zone, the dentate gyrus, and the rostromigratory stream of the postnatal mammalian brain, [26][27][28] all areas where NSC are abundant. [29][30][31] Clinically, GBM are often located in close association to such areas, 4,32 thus it is no surprise that Notch pathway components often are found aberrantly expressed in GBM and thereof derived neurosphere cultures.…”

Iterative Role of Notch Signaling in Spinal Motor Neuron Diversification

“…The Notch signaling pathway contributes to neural diversification in invertebrates and vertebrates through two principal mechanisms (Moohr, 1919; Udolph, 2012) - specification of cell fate indirectly through the regulation of the timing of neurogenesis and by direct Notch mediated regulation of cell fate determinants in asymmetrically dividing cells. In laminar regions of the vertebrate CNS, inhibition of Notch signaling typically results in premature neurogenesis and increased production of early born neuronal subtypes at the expense of later born cells (Livesey and Cepko, 2001; Nelson et al, 2007).…”

From the Eye to the Brain

“…4 B”’). These two groups of neuroblast progeny are called hemi-lineages and differ in their adult neuronal identity (Lin et al 2012, Udolph 2012, Bertet et al 2014)…”