Lef1 is required for progenitor cell identity in the zebrafish lateral line primordium

Abstract

SUMMARYThe zebrafish posterior lateral line (pLL) is a sensory system that comprises clusters of mechanosensory organs called neuromasts (NMs) that are stereotypically positioned along the surface of the trunk. The NMs are deposited by a migrating pLL primordium, which is organized into polarized rosettes (proto-NMs). During migration, mature proto-NMs are deposited from the trailing part of the primordium, while progenitor cells in the leading part give rise to new proto-NMs. Wnt signaling is active in the leading zone of the primordium and global Wnt inactivation leads to dramatic disorganization of the primordium and a loss of proto-NM formation. However, the exact cellular events that are regulated by the Wnt pathway are not known. We identified a mutant strain, lef1 nl2, that contains a lesion in the Wnt effector gene lef1. lef1 nl2 mutants lack posterior NMs and live imaging reveals that rosette renewal fails during later stages of migration. Surprisingly, the overall primordium patterning, as assayed by the expression of various markers, appears unaltered in lef1 nl2 mutants. Lineage tracing and mosaic analyses revealed that the leading cells (presumptive progenitors) move out of the primordium and are incorporated into NMs; this results in a decrease in the number of proliferating progenitor cells and eventual primordium disorganization. We concluded that Lef1 function is not required for initial primordium organization or migration, but is necessary for proto-NM renewal during later stages of pLL formation. These findings revealed a novel role for the Wnt signaling pathway during mechanosensory organ formation in zebrafish.

Lef1-dependent Wnt/β-catenin signalling drives the proliferative engine that maintains tissue homeostasis during lateral line development

“…This further supports a link between the size of the leading zone and the primordium as a whole. Our model is also consistent with data from an accompanying paper in this issue (McGraw et al, 2011), which shows that inhibition of lef1 function modifies the identity of progenitor cells in the leading edge of the primordium.…”

Fgfr-Ras-MAPK signaling is required for apical constriction via apical positioning of Rho-associated kinase during mechanosensory organ formation

“…1A). pMAPK was not detectable in the leading-most progenitor cells of the pLLp (McGraw et al, 2011). Blocking Fgfr signaling with the chemical inhibitor SU5402 (Mohammadi et al, 1997) resulted in pMAPK loss, indicating that Fgfr activity is required for MAPK cascade activation (Fig.…”

Innervation is required for sense organ development in the lateral line system of adult zebrafish

“…We confirmed the requirement for Wnt signaling by showing that heat-shock-induced expression of the Wnt-signaling antagonist Dkk reduces the number of ter2′ neuromasts and delays the formation of CLL lines. It has been reported that budding takes place normally in lef1 mutant fishes (18). This suggests that other T cell-specific factor (tcf) genes, possibly tcf7 (27), can substitute for lef1/tcf1 at later stages of development, as shown in many other sytems (reviewed in ref.…”

“…During embryonic development of the PLL, Wnt/β-catenin signaling is essential for cell proliferation in the leading region of the migrating primordium (15)(16)(17)(18). This led us to examine whether Wnt activity can be detected during stitching.…”