Regulation of PCP by the Fat signaling pathway

Matis, Maja; Axelrod, Jeffrey

doi:10.1101/gad.228098.113

Cited by 132 publications

(168 citation statements)

References 138 publications

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“…Other processes where microtubules decode inductive signals are symmetric and asymmetric stem cell divisions [303][304][305][306] and symmetric cell divisions under the control of the Wnt/planar cell polarity pathway [307][308][309]. Interestingly, the latter type of regulation is responsible for asymmetric positioning of motile cilia [19,20,310].…”

Section: Microtubules: Spindles and Centrosomesmentioning

confidence: 99%

Cytoskeletal Symmetry Breaking and Chirality: From Reconstituted Systems to Animal Development

Pohl

2015

Symmetry

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Animal development relies on repeated symmetry breaking, e.g., during axial specification, gastrulation, nervous system lateralization, lumen formation, or organ coiling. It is crucial that asymmetry increases during these processes, since this will generate higher morphological and functional specialization. On one hand, cue-dependent symmetry breaking is used during these processes which is the consequence of developmental signaling. On the other hand, cells isolated from developing animals also undergo symmetry breaking in the absence of signaling cues. These spontaneously arising asymmetries are not well understood. However, an ever growing body of evidence suggests that these asymmetries can originate from spontaneous symmetry breaking and self-organization of molecular assemblies into polarized entities on mesoscopic scales. Recent discoveries will be highlighted and it will be discussed how actomyosin and microtubule networks serve as common biomechanical systems with inherent abilities to drive spontaneous symmetry breaking.

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Section: Microtubules: Spindles and Centrosomesmentioning

confidence: 99%

Cytoskeletal Symmetry Breaking and Chirality: From Reconstituted Systems to Animal Development

Pohl

2015

Symmetry

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“…Fat4 and Dchs1 are the vertebrate orthologs of Drosophila Fat and Dachsous (Ds), respectively, which, together with the novel Golgi kinase Four-jointed (Fj), regulate planar cell polarity (PCP) and growth via the Hippo pathway (Staley and Irvine, 2012;Matis and Axelrod, 2013). PCP is classically described as the coordinated cell polarity within an epithelium, but in vertebrates has also been shown to control cellular rearrangements and behaviours within mesenchymal tissues (Goodrich and Strutt, 2011).…”

Section: Introductionmentioning

confidence: 99%

Fat4-Dchs1 signalling controls cell proliferation in developing vertebrae

et al. 2016

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The protocadherins Fat4 and Dchs1 act as a receptor-ligand pair to regulate many developmental processes in mice and humans, including development of the vertebrae. Based on conservation of function between Drosophila and mammals, Fat4-Dchs1 signalling has been proposed to regulate planar cell polarity (PCP) and activity of the Hippo effectors Yap and Taz, which regulate cell proliferation, survival and differentiation. There is strong evidence for Fat regulation of PCP in mammals but the link with the Hippo pathway is unclear. In Fat4 −/− and Dchs1 −/− mice, many vertebrae are split along the midline and fused across the anterior-posterior axis, suggesting that these defects might arise due to altered cell polarity and/or changes in cell proliferation/differentiation. We show that the somite and sclerotome are specified appropriately, the transcriptional network that drives early chondrogenesis is intact, and that cell polarity within the sclerotome is unperturbed. We find that the key defect in Fat4 and Dchs1 mutant mice is decreased proliferation in the early sclerotome. This results in fewer chondrogenic cells within the developing vertebral body, which fail to condense appropriately along the midline. Analysis of Fat4;Yap and Fat4;Taz double mutants, and expression of their transcriptional target Ctgf, indicates that Fat4-Dchs1 regulates vertebral development independently of Yap and Taz. Thus, we have identified a new pathway crucial for the development of the vertebrae and our data indicate that novel mechanisms of Fat4-Dchs1 signalling have evolved to control cell proliferation within the developing vertebrae.

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“…This pathway also plays a key role in PCP in a variety of vertebrate tissues (and processes), such as the inner ear (Ezan and Montcouquiol, 2013;Montcouquiol et al, 2003;Wang et al, 2005), murine fur (Chang and Nathans, 2013;Wang et al, 2006;Wang and Nathans, 2007), murine respiratory system (Vladar et al, 2012) and mediolateral cell polarization and convergent extension during vertebrate embryogenesis (Goto and Keller, 2002;Heisenberg et al, 2000;Jessen et al, 2002;Tada and Smith, 2000;Wallingford et al, 2001). A second key regulator of PCP is the dachsous/fat pathway Casal et al, 2006;Harumoto et al, 2010;Ma et al, 2003;Matis and Axelrod, 2013;Merkel et al, 2014;Olofsson et al, 2014;Yang et al, 2002), which interacts with the fz/stan pathway. Additional genes have also been found to be important for fly PCP but how they relate to the fz/stan genes remains unclear (e.g.…”

Section: Introductionmentioning

confidence: 99%

TheDrosophilaplanar polarity genemultiple wing hairsdirectly regulates the actin cytoskeleton

Schafer

Adler

2015

Development

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The evolutionarily conserved frizzled/starry night (fz/stan) pathway regulates planar cell polarity (PCP) in vertebrates and invertebrates. This pathway has been extensively studied in the Drosophila wing, where it is manifested by an array of distally pointing cuticular hairs. Using in vivo imaging we found that, early in hair growth, cells have multiple actin bundles and hairs that subsequently fuse into a single growing hair. The downstream PCP gene multiple wing hairs (mwh) plays a key role in this process and acts to antagonize the actin cytoskeleton. In mwh mutants hair initiation is not limited to a small region at the distal edge of pupal wing cells as in wild type, resulting in multiple hairs with aberrant polarity. Extra actin bundles/hairs are formed and do not completely fuse, in contrast to wild type. As development proceeded additional hairs continued to form, further increasing hair number. We identified a fragment of Mwh with in vivo rescue activity and that bound and bundled F-actin filaments and inhibited actin polymerization in in vitro actin assays. The loss of these activities can explain the mwh mutant phenotype. Our data suggest a model whereby, prior to hair initiation, proximally localized Mwh inhibits actin polymerization resulting in polarized activation of the cytoskeleton and hair formation on the distal side of wing cells. During hair growth Mwh is found in growing hairs, where we suggest it functions to promote the fusion of actin bundles and inhibit the formation of additional actin bundles that could lead to extra hairs.

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Regulation of PCP by the Fat signaling pathway

Cited by 132 publications

References 138 publications

Cytoskeletal Symmetry Breaking and Chirality: From Reconstituted Systems to Animal Development

Cytoskeletal Symmetry Breaking and Chirality: From Reconstituted Systems to Animal Development

Fat4-Dchs1 signalling controls cell proliferation in developing vertebrae

TheDrosophilaplanar polarity genemultiple wing hairsdirectly regulates the actin cytoskeleton

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