Responses of hair follicle–associated structures to loss of planar cell polarity signaling

Chang, Haiyan; Nathans, Jeremy

doi:10.1073/pnas.1301430110

Cited by 30 publications

(39 citation statements)

References 35 publications

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“…In Fz6 −/− mice, the anterior-posterior polarity of the Merkel cell cluster is lost and the Merkel cells are arranged in a complete circle (Chang and Nathans, 2013;Fig. 2B).…”

Section: Alleles For Ubiquitous Production Of Fz3 and Fz6mentioning

confidence: 99%

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Partial interchangeability of Fz3 and Fz6 in tissue polarity signaling for epithelial orientation and axon growth and guidance

et al. 2014

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In mammals, a set of anatomically diverse polarity processesincluding axon growth and guidance, hair follicle orientation, and stereociliary bundle orientation in inner ear sensory hair cells -appear to be mechanistically related, as judged by their dependence on vertebrate homologues of core tissue polarity/planar cell polarity (PCP) genes in Drosophila. To explore more deeply the mechanistic similarities between different polarity processes, we have determined the extent to which frizzled 3 (Fz3) can rescue the hair follicle and Merkel cell polarity defects in frizzled 6-null (Fz6 −/− ) mice, and, reciprocally, the extent to which Fz6 can rescue the axon growth and guidance defects in Fz3 −/− mice. These experiments reveal full rescue of the Fz6 −/− phenotype by Fz3 and partial rescue of the Fz3 −/− phenotype by Fz6, implying that these two proteins are likely to act in a conserved manner in these two contexts. Stimulated by these observations, we searched for additional anatomical structures that exhibit macroscopic polarity and that might plausibly use Fz3 and/or Fz6 signaling. This search has revealed a hitherto unappreciated pattern of papillae on the dorsal surface of the tongue that depends, at least in part, on redundant signaling by Fz3 and Fz6. Taken together, these experiments provide compelling evidence for a close mechanistic relationship between multiple anatomically diverse polarity processes.

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“…In Fz6 −/− mice, the anterior-posterior polarity of the Merkel cell cluster is lost and the Merkel cells are arranged in a complete circle (Chang and Nathans, 2013;Fig. 2B).…”

Section: Alleles For Ubiquitous Production Of Fz3 and Fz6mentioning

confidence: 99%

“…The procedures for preparation and processing of skin whole mounts for Merkel cells immunostaining and imaging of hair follicles based on melanin content are described by Chang and Nathans (2013) and Chang et al (2014).…”

Section: Skin Whole Mountsmentioning

confidence: 99%

Partial interchangeability of Fz3 and Fz6 in tissue polarity signaling for epithelial orientation and axon growth and guidance

et al. 2014

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“…Genetic studies identified the frizzled ( fz)/starry night (stan) pathway as an essential regulator of PCP in a number of Drosophila tissues/body regions, such as the wing, eye and abdomen (Adler, 1992;Gho and Schweisguth, 1998;Gubb and Garcia-Bellido, 1982;Held et al, 1986;Lawrence et al, 2004;Vinson and Adler, 1987;Wong and Adler, 1993;Zheng et al, 1995). 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.…”

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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“…This tissue planar cell polarity (PCP) is dramatic in the cuticle of insects such as Drosophila, which is decorated with arrays of hairs and sensory bristles. Tissue polarity in Drosophila is under the control of the frizzled ( fz ) /starry night ( stan ) signaling pathway and in recent years it has become clear that this conserved pathway also controls planar polarity in many aspects of vertebrate development (Goodrich and Strutt, 2011; Wang and Nathans, 2007) including cell and tissue movements during gastrulation (Goto and Keller, 2002; Jessen et al, 2002; Takeuchi et al, 2003; Wallingford et al., 2001), the differentiation of stereocilia in the inner ear (Montcouquiol et al, 2003; Wang et al, 2005; Wang et al, 2006), the morphogenesis of the fur of mice(Chang and Nathans, 2013), kidney development (Babayeva et al., 2013; Goggolidou, 2013) and the polarity of the cilia in the respiratory epithelium (Vladar et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

The proteins encoded by the Drosophila Planar Polarity Effector genes inturned, fuzzy and fritz interact physically and can re-pattern the accumulation of “upstream” Planar Cell Polarity proteins

Wang

Yan

Lee

et al. 2014

Developmental Biology

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The frizzled/starry night pathway regulates planar cell polarity in a wide variety of tissues in many types of animals. It was discovered and has been most intensively studied in the Drosophila wing where it controls the formation of the array of distally pointing hairs that cover the wing. The pathway does this by restricting the activation of the cytoskeleton to the distal edge of wing cells. This results in hairs initiating at the distal edge and growing in the distal direction. All of the proteins encoded by genes in the pathway accumulate asymmetrically in wing cells. The pathway is a hierarchy with the Planar Cell Polarity (PCP) genes (aka the core genes) functioning as a group upstream of the Planar Polarity Effector (PPE) genes which in turn function as a group upstream of multiple wing hairs. Upstream proteins, such as Frizzled accumulate on either the distal and/or proximal edges of wing cells. Downstream PPE proteins accumulate on the proximal edge under the instruction of the upstream proteins. A variety of types of data support this hierarchy, however, we have found that when over expressed the PPE proteins can alter both the subcellular location and level of accumulation of the upstream proteins. Thus, the epistatic relationship is context dependent. We further show that the PPE proteins interact physically and can modulate the accumulation of each other in wing cells. We also find that over expression of Frtz results in a marked delay in hair initiation suggesting that it has a separate role/activity in regulating the cytoskeleton that is not shared by other members of the group.

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Responses of hair follicle–associated structures to loss of planar cell polarity signaling

Cited by 30 publications

References 35 publications

Partial interchangeability of Fz3 and Fz6 in tissue polarity signaling for epithelial orientation and axon growth and guidance

Partial interchangeability of Fz3 and Fz6 in tissue polarity signaling for epithelial orientation and axon growth and guidance

TheDrosophilaplanar polarity genemultiple wing hairsdirectly regulates the actin cytoskeleton

The proteins encoded by the Drosophila Planar Polarity Effector genes inturned, fuzzy and fritz interact physically and can re-pattern the accumulation of “upstream” Planar Cell Polarity proteins

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