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.
Highlights
Organ morphogenesis relies on the integration of complex processes, such as cell migration, cell shape changes and cell specification to generate the correct three-dimensional geometry necessary for function
Constitutive activation of Notch or Wnt signaling generates larger sensory organs When we constitutively activate Notch signaling in the lateral line by driving the NICD in (Tg(cldnB: lynGFP);Tg(cldnB:gal4) x Tg(UAS:nicd)) embryos, we observe that deposited neuromasts are substantially larger than in sibling embryos (Figure 1A–B’, Figure 1—figure supplement 1A–A’; Video 1)
Heat-shock activation of Notch signaling after the primordium and ganglion have separated significantly increases the neuromast cell number (Figure 1Q–R’, Figure 1—figure supplement 1E). These results indicate that, the primordium size determines the maximum size of an enlarged neuromast, the increased NICD neuromast size is independent of the early role of Notch in allocating cells to the primordium
Summary
Organ morphogenesis relies on the integration of complex processes, such as cell migration, cell shape changes and cell specification to generate the correct three-dimensional geometry necessary for function. These cell behaviors must be coupled with mechanisms that regulate the final size of the organ for correct integration into the organism. The zebrafish lateral line is a powerful model to study sensory organ morphogenesis, as it develops superficially in the skin and is amenable to experimental manipulation and in vivo imaging. The lateral line system on the trunk develops from an ectodermal placode posterior to the ear that migrates to the tail tip.
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