Planar cell polarity effector gene Intu regulates cell fate-specific differentiation of keratinocytes through the primary cilia

Dai, Dongfang; Li, L; Huebner, Aaron J.; Zeng, Huiqing; Guevara, Elizabeth; Claypool, David J.; Liu, Aimin; Chen, J

doi:10.1038/cdd.2012.104

Cited by 21 publications

(35 citation statements)

References 61 publications

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“…S9B). These cells are proposed to be keratinocytes that are committed to the follicular fate but have failed to develop into hair follicles because of disrupted Hh signaling or primary cilia formation (Chen et al, 2015;Chiang et al, 1999;Dai et al, 2013Dai et al, , 2011Gat et al, 1998;Mill et al, 2003;St-Jacques et al, 1998). Thus, the congregation of these ciliated keratinocytes in the epidermal invaginations of Ift27 −/− skin transplants not only confirmed this speculation but also strengthened our previous observation that Ift27 is essential for Hh signaling (Fig.…”

Section: Hh Signaling Is Perturbed Insupporting

confidence: 80%

“…Interestingly, when Hh or ciliary genes were disrupted in a tissue-specific fashion, i.e. in the epidermal lineage (Dai et al, 2013) or in mesenchymal cells (Lehman et al, 2009;Woo et al, 2012), the resultant phenotypes were almost identical to those in germline mutants (Chen et al, 2015;Chiang et al, 1999;Dai et al, 2011;Gat et al, 1998;Mill et al, 2003;St-Jacques et al, 1998;Woo et al, 2012). These findings strongly suggest that disrupting Hh signaling or cilia formation/function in either or both tissue compartments of the hair follicle will, individually or collectively, contribute to hair follicle morphogenesis defects.…”

Section: Discussionmentioning

confidence: 83%

“…In addition, the primary cilium is essential for the proteolytic processing of Gli factors into transcriptional repressors in the absence of the ligand (Haycraft et al, 2005;Huangfu and Anderson, 2005). A number of recent studies demonstrated that disrupting cilia formation results in developmental arrest of hair follicles by suppressing Hh signaling (Chen et al, 2015;Dai et al, 2013Dai et al, , 2011Lehman et al, 2009). These studies confirmed the integral role of primary cilia in mediating the epithelial-mesenchymal crosstalk required for hair follicle morphogenesis.…”

Section: Introductionmentioning

confidence: 71%

“…Activation of the Hh signaling pathway requires the primary cilia. A number of recent studies unequivocally demonstrated that the primary cilium is essential for hair follicle morphogenesis; disrupting ciliogenesis results in the arrest of hair follicle development due to disrupted Hh signaling (Chen et al, 2015;Dai et al, 2013Dai et al, , 2011Lehman et al, 2009). Thus, the formation of the ciliary axoneme is prerequisite for its function; disrupting cilia formation inevitably disrupts its function, including the transduction of Hh signals.…”

Section: Discussionmentioning

confidence: 99%

“…Quantitative RT-PCR and western blotting RNA isolation and quantitative RT-PCR analyses were performed as described previously (Dai et al, 2013). The following probes were used for TaqMan analysis: Ift27, ABI Mm00508912_m1; Ptch1, Mm00436026_m1; Gli1, Mm00494645_m1; Gli2, Mm01293111_m1; Smo, Mm01162710_m1; and Actb, Mm00607939_m1 (Life Technologies).…”

Section: Cell Culture and In Vitro Assaysmentioning

confidence: 99%

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Intraflagellar transport 27 is essential for hedgehog signaling but dispensable for ciliogenesis during hair follicle morphogenesis

Yang

Eguether

et al. 2015

Development

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Hair follicle morphogenesis requires precisely controlled reciprocal communications, including hedgehog (Hh) signaling. Activation of the Hh signaling pathway relies on the primary cilium. Disrupting ciliogenesis results in hair follicle morphogenesis defects due to attenuated Hh signaling; however, the loss of cilia makes it impossible to determine whether hair follicle phenotypes in these cilia mutants are caused by the loss of cilia, disruption of Hh signaling, or a combination of these events. In this study, we characterized the function of Ift27, which encodes a subunit of intraflagellar transport (IFT) complex B. Hair follicle morphogenesis of Ift27-null mice was severely impaired, reminiscent of phenotypes observed in cilia and Hh mutants. Furthermore, the Hh signaling pathway was attenuated in Ift27 mutants, which was in association with abnormal ciliary trafficking of SMO and GLI2, and impaired processing of Gli transcription factors; however, formation of the ciliary axoneme was unaffected. The ciliary localization of IFT25 (HSPB11), the binding partner of IFT27, was disrupted in Ift27 mutant cells, and Ift25-null mice displayed hair follicle phenotypes similar to those of Ift27 mutants. These data suggest that Ift27 and Ift25 operate in a genetically and functionally dependent manner during hair follicle morphogenesis. This study suggests that the molecular trafficking machineries underlying ciliogenesis and Hh signaling can be segregated, thereby providing important insights into new avenues of inhibiting Hh signaling, which might be adopted in the development of targeted therapies for Hh-dependent cancers, such as basal cell carcinoma.

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Section: Hh Signaling Is Perturbed Insupporting

confidence: 80%

Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Cell Culture and In Vitro Assaysmentioning

confidence: 99%

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Intraflagellar transport 27 is essential for hedgehog signaling but dispensable for ciliogenesis during hair follicle morphogenesis

Yang

Eguether

et al. 2015

Development

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Gorab Is Required for Dermal Condensate Cells to Respond to Hedgehog Signals during Hair Follicle Morphogenesis

Liu

Snedecor

Choi

et al. 2016

Journal of Investigative Dermatology

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GORAB is a golgin that localizes predominantly at the Golgi apparatus and physically interacts with small GTPases. GORAB is ubiquitously expressed in mammalian tissues, including the skin. However, the biological function of this golgin in skin is unknown. Here, we report that disrupting the expression of the Gorab gene in mice results in hair follicle morphogenesis defects that were characterized by impaired follicular keratinocyte differentiation. This hair follicle phenotype was associated with markedly suppressed hedgehog (Hh) signaling pathway in dermal condensates in vivo. Gorab-deficient dermal mesenchymal cells also displayed significantly reduced capability to respond to Hh pathway activation in vitro. Furthermore, we found that the formation of primary cilium, a cellular organelle that is essential for the Hh pathway, was impaired in mutant dermal papilla cells, suggesting that Gorab may be required for the Hh pathway through facilitating the formation of primary cilia. Thus, data obtained from this study provided insight onto the biological functions of Gorab during embryonic morphogenesis of skin in which Hh signaling and primary cilia exert important functions.

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Overexpression of MYB in the Skin Induces Alopecia and Epidermal Hyperplasia

Song

Jiang

et al. 2020

Journal of Investigative Dermatology

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Skin homeostasis is controlled by a complex interplay between tightly regulated transcription factors and signaling pathways. MYB is a transcription factor expressed in hair follicle progenitor cells and found overexpressed in adnexal skin tumors. However, the biological consequences of deregulated MYB expression in the skin remain poorly understood. To address this, we generated transgenic mice that overexpress MYB in epidermal and follicular keratinocytes. These mice exhibited a normal hair coat after birth but gradually developed alopecia, accompanied by altered follicular differentiation, disrupted hair cycle, and a marked depletion of hair follicle stem cells. Additionally, transgenic mice developed massive epidermal hyperplasia and hyperkeratosis. Global expression profiling not only confirmed that the skin of these mice exhibited transcriptomic features of alopecia and epidermal differentiation, but also revealed features of psoriasis and the inflammatory response. The latter was further confirmed by the increased T-cell infiltration found in the skin of transgenic mice. Overall, these results suggest that tight regulation of MYB expression in the skin is critical to maintain skin homeostasis.

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Planar cell polarity effector gene Intu regulates cell fate-specific differentiation of keratinocytes through the primary cilia

Cited by 21 publications

References 61 publications

Intraflagellar transport 27 is essential for hedgehog signaling but dispensable for ciliogenesis during hair follicle morphogenesis

Intraflagellar transport 27 is essential for hedgehog signaling but dispensable for ciliogenesis during hair follicle morphogenesis

Gorab Is Required for Dermal Condensate Cells to Respond to Hedgehog Signals during Hair Follicle Morphogenesis

Overexpression of MYB in the Skin Induces Alopecia and Epidermal Hyperplasia

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