Planar cell polarity signalling regulates cell adhesion properties in progenitors of the zebrafish laterality organ

Oteíza, Pablo; Köppen, Mathias; Krieg, Michael; Pulgar, Eduardo; Farias, Cecilia; Melo, Cristina; Preibisch, Stephan; Müller, Daniel J.; Tada, Masazumi; Härtel, Steffen; Heisenberg, Carl‐Philipp; Concha, Miguel L.

doi:10.1242/dev.049981

Cited by 63 publications

(75 citation statements)

References 62 publications

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“…However, in these phenotypes, some DFCs remained capable of interacting with others to form small groups of cells, implying that other factor(s) may contribute to DFC clustering. It has been reported that integrin αV and integrin β1b have a role in DFC clustering (26) and that planar cell polarity signaling regulates cell adhesion between DFCs (27). Additional experiments to clarify the relationship between FGF signaling and integrins or planar cell polarity signaling during DFC cluster formation will be important to understand the entire mechanism underlying DFC cluster formation.…”

Section: Discussionmentioning

confidence: 99%

Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis

Matsui

Thitamadee

Murata

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The assembly of progenitor cells is a crucial step for organ formation during vertebrate development. Kupffer's vesicle (KV), a key organ required for the left-right asymmetric body plan in zebrafish, is generated from a cluster of ∼20 dorsal forerunner cells (DFCs). Although several genes are known to be involved in KV formation, how DFC clustering is regulated and how cluster formation then contributes to KV formation remain unclear. Here we show that positive feedback regulation of FGF signaling by Canopy1 (Cnpy1) controls DFC clustering. Cnpy1 positively regulates FGF signals within DFCs, which in turn promote Cadherin1-mediated cell adhesion between adjacent DFCs to sustain cell cluster formation. When this FGF positive feedback loop is disrupted, the DFC cluster fails to form, eventually leading to KV malformation and defects in the establishment of laterality. Our results therefore uncover both a previously unidentified role of FGF signaling during vertebrate organogenesis and a regulatory mechanism underlying cell cluster formation, which is an indispensable step for formation of a functional KV and establishment of the left-right asymmetric body plan.left-right patterning | ciliogenesis F ibroblast growth factor (FGF) signaling plays crucial roles in multiple morphogenetic processes of vertebrate development, including gastrulation movement, mesoderm formation, and leftright (LR) patterning (1-3). Because gain or loss of function of FGF signaling results in morphological changes in the embryo, some mechanism must ensure appropriate FGF signal levels in space and time for proper morphogenesis throughout development. FGF effectors acting as positive or negative regulators show a wide range of expression patterns and activities, contributing to the precise regulation of FGF signal activity (1, 4). Although most effectors identified to date act as negative regulators of FGF signaling, a few that positively regulate FGF activity have been reported (1, 4).We recently identified in zebrafish a positive regulator of FGF signaling named canopy1 (cnpy1), which is required for maintenance of the midbrain-hindbrain boundary (MHB) (5). Expression of cnpy1 was restricted to the MHB at late-somitogenesis stages, whereas cnpy1 was broadly distributed in earlier embryos (5) (SI Appendix, Fig. S1A), suggesting an additional role(s) for Cnpy1-mediated FGF signaling beyond the regulation of MHB formation. In this study, we characterize cnpy1 in detail during early zebrafish development and show that a Cnpy1-mediated positive feedback loop of FGF signaling promotes cell cluster formation between dorsal forerunner cells (DFCs) during gastrulation. We also demonstrate that the failure of DFCs to cluster when this FGF positive loop is disrupted eventually leads to Kupffer's vesicle (KV) malformation and randomization of LR asymmetric patterning. Results Positive Feedback Loop of FGF Signaling Mediated by Cnpy1 IsActivated Specifically in DFCs During Zebrafish Gastrulation. To reveal the role of Cnpy1-mediated FGF signaling in ...

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Section: Discussionmentioning

confidence: 99%

Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis

Matsui

Thitamadee

Murata

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Lgl2 and E-cadherin have been previously shown to function antagonistically to control hemidesmosome formation in basal epidermal cells , and membrane localization of E-cadherin in the epidermis was disrupted in lgl2 mutant embryos (Reischauer et al, 2009). In addition, knockdown of E-cadherin in the DFC/KV cell lineage resulted in KV morphogenesis defects similar to those observed in Lgl2 MO embryos, including altered DFC clustering and small KV lumen size (Matsui et al, 2011;Oteíza et al, 2008;Oteiza et al, 2010). To study the relationship of Lgl2 with Ecadherin in KV, we performed immunostaining using E-cadherin antibodies and compared control and Lgl2 MO embryos.…”

Section: Research Articlementioning

confidence: 94%

“…However, Lgl2:EYFP was found to localize near the adherens junction protein E-cadherin (Fig. 4B), which is known to play important roles in KV development (Matsui et al, 2011;Oteíza et al, 2008;Oteiza et al, 2010). Because the relationship between lumenogenesis and ciliogenic programs remain poorly understood, such that reduced ciliogenesis (A) Asymmetric heart looping at 2 dpf visualized in Tg(cmlc2:GFP) transgenic embryos that express GFP in the heart.…”

Section: Research Articlementioning

confidence: 99%

Lethal giant larvae 2 regulates development of the ciliated organ Kupffer’s vesicle

et al. 2013

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SUMMARYMotile cilia perform crucial functions during embryonic development and throughout adult life. Development of organs containing motile cilia involves regulation of cilia formation (ciliogenesis) and formation of a luminal space (lumenogenesis) in which cilia generate fluid flows. Control of ciliogenesis and lumenogenesis is not yet fully understood, and it remains unclear whether these processes are coupled. In the zebrafish embryo, lethal giant larvae 2 (lgl2) is expressed prominently in ciliated organs. Lgl proteins are involved in establishing cell polarity and have been implicated in vesicle trafficking. Here, we identified a role for Lgl2 in development of ciliated epithelia in Kupffer's vesicle, which directs left-right asymmetry of the embryo; the otic vesicles, which give rise to the inner ear; and the pronephric ducts of the kidney. Using Kupffer's vesicle as a model ciliated organ, we found that depletion of Lgl2 disrupted lumen formation and reduced cilia number and length. Immunofluorescence and time-lapse imaging of Kupffer's vesicle morphogenesis in Lgl2-deficient embryos suggested cell adhesion defects and revealed loss of the adherens junction component E-cadherin at lateral membranes. Genetic interaction experiments indicate that Lgl2 interacts with Rab11a to regulate E-cadherin and mediate lumen formation that is uncoupled from cilia formation. These results uncover new roles and interactions for Lgl2 that are crucial for both lumenogenesis and ciliogenesis and indicate that these processes are genetically separable in zebrafish.

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“…Ecadherin is shown to play an essential role in zebrafish epiboly, a process in which the blastoderm and the yolk syncytial layer undergo radial intercalation to spread out and envelop the yolk (Kane et al, 2005;Shimizu et al, 2005). Non-canonical Wnt5 and Wnt11 can regulate the expression pattern of cadherins (Bradley and Drissi, 2011;Nagy et al, 2010); PCP signaling regulates cell adhesion properties of the zebrafish laterality organ (Oteiza et al, 2010); and PCP protein Vangl2 interacts with Rac1 to regulate AJs in the developing neural tube in mice (Lindqvist et al, 2010). Here, we showed that the levels of E-cadherin and N-cadherin are reduced significantly in p120 CKO/CKO animals (Fig.…”

Section: Distinct Molecular Regulation Of Epithelial Ce and Pcp In Vementioning

confidence: 99%

Regulation of cochlear convergent extension by the vertebrate planar cell polarity pathway is dependent on p120-catenin

et al. 2012

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SUMMARYThe vertebrate planar cell polarity (PCP) pathway consists of conserved PCP and ciliary genes. During development, the PCP pathway regulates convergent extension (CE) and uniform orientation of sensory hair cells in the cochlea. It is not clear how these diverse morphogenetic processes are regulated by a common set of PCP genes. Here, we show that cellular contacts and geometry change drastically and that the dynamic expression of N-cadherin and E-cadherin demarcates sharp boundaries during cochlear extension. The conditional knockout of a component of the adherens junctions, p120-catenin, leads to the reduction of E-cadherin and N-cadherin and to characteristic cochlear CE defects but not misorientation of hair cells. The specific CE defects in p120-catenin mutants are in contrast to associated CE and hair cell misorientation defects observed in common PCP gene mutants. Moreover, the loss-of-function of a conserved PCP gene, Vangl2, alters the dynamic distribution of N-cadherin and Ecadherin in the cochlea and causes similar abnormalities in cellular morphology to those found in p120-catenin mutants. Conversely, we found that Pcdh15 interacts genetically with PCP genes to regulate the formation of polar hair bundles, but not CE defects in the cochlea. Together, these results indicate that the vertebrate PCP pathway regulates CE and hair cell polarity independently and that a p120-catenin-dependent mechanism regulates CE of the cochlea.

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Planar cell polarity signalling regulates cell adhesion properties in progenitors of the zebrafish laterality organ

Cited by 63 publications

References 62 publications

Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis

Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis

Lethal giant larvae 2 regulates development of the ciliated organ Kupffer’s vesicle

Regulation of cochlear convergent extension by the vertebrate planar cell polarity pathway is dependent on p120-catenin

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