Do as I say, Not(ch) as I do: Lateral control of cell fate

Abstract

Breaking symmetry in populations of uniform cells, to induce adoption of an alternative cell fate, is an essential developmental mechanism. Similarly, domain and boundary establishment are crucial steps to forming organs during development. Notch signaling is a pathway ideally suited to mediating precise patterning cues, as both receptors and ligands are membrane-bound and can thus act as a precise switch to toggle cell fates on or off. Fine-tuning of signaling by positive or negative feedback mechanisms dictate whether signaling results in lateral induction or lateral inhibition, respectively, allowing Notch to either induce entire regions of cell specification, or dictate binary fate choices. Furthermore, pathway activity is modulated by Fringe modification of receptors or ligands, co-expression of receptors with ligands, mode of ligand presentation, and cell surface area in contact. In this review, we describe how Notch signaling is fine-tuned to mediate lateral induction or lateral inhibition cues, and discuss examples from C.elegans, D. melanogaster and M. musculus. Identifying the cellular machinery dictating the choice between lateral induction and lateral inhibition highlights the versatility of the Notch signaling pathway in development.

FGF signaling patterns cell fate at the interface between tendon and bone

“…We show evidence that Fgfr2-Fgf2 signaling regulates cell fate at the tendon-bone interface by spatially deploying Notch2 signaling. Notch signaling is a key regulator of binary cell fate choice, and the cellular outcomes of Notch-Jagged and Notch-Delta signaling are distinct (Sjoqvist and Andersson, 2019). Notch activation by Jagged induces neighboring cells within a pool of equivalent progenitors to adopt a common cell fate through lateral induction.…”

DLK1, Notch Signaling and the Timing of Puberty

“…2a). 44,45,47,51 Once in the nucleus, the NICD functions as a transcriptional activator, interacting with RBPJk and other coactivators of the Mastermind-like family, as well as the histone acetyl transferase p300, to initiate transcription of Notch target genes (►Fig. 2a).…”

A new role for Notch in the control of polarity and asymmetric cell division of developing T cells

“…Fate bifurcation is driven by various means, including random differences in the daughters, different positional cues, or controlled segregation of fate determinants differentially into the two daughter cells, a process termed Asymmetric Cell Division (ACD) (Dewey et al, 2015;Schweisguth, 2015;Venkei et al, 2018). A common mediator of fate bifurcation, which uses all of these processes, is the Notch signalling pathway (Artavanis-Tsakonas et al, 1999;Fortini, 2009;Liu et al, 2017;Sjoqvist et al, 2017). Notch is a transmembrane receptor that responds to ligands belonging to the Delta and Jagged family, which are present on adjacent cells (Bray, 2016).…”