Proliferation-independent regulation of organ size by Fgf/Notch signaling

Abstract

Organ morphogenesis depends on the precise orchestration of cell migration, cell shape changes and cell adhesion. We demonstrate that Notch signaling is an integral part of the Wnt and Fgf signaling feedback loop coordinating cell migration and the self-organization of rosette-shaped sensory organs in the zebrafish lateral line system. We show that Notch signaling acts downstream of Fgf signaling to not only inhibit hair cell differentiation but also to induce and maintain stable epithelial rosettes. Ectopic Notch expression causes a significant increase in organ size independently of proliferation and the Hippo pathway. Transplantation and RNASeq analyses revealed that Notch signaling induces apical junctional complex genes that regulate cell adhesion and apical constriction. Our analysis also demonstrates that in the absence of patterning cues normally provided by a Wnt/Fgf signaling system, rosettes still self-organize in the presence of Notch signaling.DOI: http://dx.doi.org/10.7554/eLife.21049.001

Mouse Model of Alagille Syndrome and Mechanisms of Jagged1 Missense Mutations

“…CSL, the canonical Notch transcription factor, in embryonic stem cells disrupts neural rosettes, 35 a lumenized and polarized colony of neural cells modeling the neural tube in vitro. Similarly, in the zebrafish lateral line, Notch is required for apical constriction of proneuromast rosettes, 36 and regulates apical junction-associated genes, which together with our results, indicates a more general interaction between Notch and the cell polarity machinery.…”

Notch signaling pathway regulates cell cycle in proliferating hepatocytes involved in liver regeneration

“…The Notch signaling pathway, highly conserved and ubiquitously expressed in tissues, has a wide range of regulatory roles in cell genesis, development, differentiation, proliferation, and apoptosis . In mammals, Notch system consists of four transmembrane receptors (Notch‐1, Notch‐2, Notch‐3, and Notch‐4) and five ligands belonging to the Jagged (Jagged‐1 and Jagged‐2) and Delta‐like (Dll‐1, Dll‐3, and Dll‐4) families .…”

Notch and Fgf signaling during electrosensory versus mechanosensory lateral line organ development in a non-teleost ray-finned fish

“…Fgf10 binds Fgfr1 in the surrounding cells, resulting in the maintenance of Notch3 expression, which in turn responds to the Notch ligands from the hair cell progenitor by blocking Atoh1 expression (preventing adoption of a hair cell fate). Fgf and Notch signaling pathway activity in the supporting cells also promotes apical constriction and cell adhesion, leading to epithelial rosette formation ( Matsuda and Chitnis, 2010 , Kozlovskaja-Gumbrienė et al, 2017 ).…”