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Keratinocyte-Specific Ablation of RIPK4 Allows Epidermal Cornification but Impairs Skin Barrier Formation

Corinne Urwyler (UGent) , Giel Tanghe (UGent) , Kirsten Leurs, Barbara Gilbert (UGent) , Riet De Rycke (UGent) , Michiel De Bruyne (UGent) , Saskia Lippens (UGent) , Sona Bartunkova (UGent) , Philippe De Groote (UGent) , Carien Niessen, et al.
(2018) JOURNAL OF INVESTIGATIVE DERMATOLOGY. 138(6). p.1268-1278
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Abstract
In humans, receptor-interacting protein kinase 4 (RIPK4) mutations can lead to the autosomal recessive Bartsocas-Papas and popliteal pterygium syndromes, which are characterized by severe skin defects, pterygia, as well as clefting. We show here that the epithelial fusions observed in RIPK4 full knockout (KO) mice are E-cadherin dependent, as keratinocyte-specific deletion of E-cadherin in RIPK4 full KO mice rescued the tail-to-body fusion and fusion of oral epithelia. To elucidate RIPK4 function in epidermal differentiation and development, we generated epidermis-specific RIPK4 KO mice (RIPK4 EKO). In contrast to RIPK4 full KO epidermis, RIPK4 EKO epidermis was normally stratified and the outside-in skin barrier in RIPK4 EKO mice was largely intact at the trunk, in contrast to the skin covering the head and the outer end of the extremities. However, RIPK4 EKO mice die shortly after birth due to excessive water loss because of loss of tight junction protein claudin-1 localization at the cell membrane, which results in tight junction leakiness. In contrast, mice with keratinocyte-specific RIPK4 deletion during adult life remain viable. Furthermore, our data indicate that epidermis-specific deletion of RIPK4 results in delayed keratinization and stratum corneum maturation and altered lipid organization and is thus indispensable during embryonic development for the formation of a functional inside-out epidermal barrier.
Keywords
BARTSOCAS-PAPAS SYNDROME, KAPPA-B ACTIVATION, STRATUM-CORNEUM, TIGHT, JUNCTIONS, PROTEIN-KINASE, CORNIFIED ENVELOPE, MICE, DIFFERENTIATION, DEFICIENT, GLUCOSYLCERAMIDES

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MLA
Urwyler, Corinne, et al. “Keratinocyte-Specific Ablation of RIPK4 Allows Epidermal Cornification but Impairs Skin Barrier Formation.” JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 138, no. 6, Elsevier Science Inc, 2018, pp. 1268–78, doi:10.1016/j.jid.2017.12.031.
APA
Urwyler, C., Tanghe, G., Leurs, K., Gilbert, B., De Rycke, R., De Bruyne, M., … Declercq, W. (2018). Keratinocyte-Specific Ablation of RIPK4 Allows Epidermal Cornification but Impairs Skin Barrier Formation. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 138(6), 1268–1278. https://doi.org/10.1016/j.jid.2017.12.031
Chicago author-date
Urwyler, Corinne, Giel Tanghe, Kirsten Leurs, Barbara Gilbert, Riet De Rycke, Michiel De Bruyne, Saskia Lippens, et al. 2018. “Keratinocyte-Specific Ablation of RIPK4 Allows Epidermal Cornification but Impairs Skin Barrier Formation.” JOURNAL OF INVESTIGATIVE DERMATOLOGY 138 (6): 1268–78. https://doi.org/10.1016/j.jid.2017.12.031.
Chicago author-date (all authors)
Urwyler, Corinne, Giel Tanghe, Kirsten Leurs, Barbara Gilbert, Riet De Rycke, Michiel De Bruyne, Saskia Lippens, Sona Bartunkova, Philippe De Groote, Carien Niessen, Marek Haftek, Peter Vandenabeele, and Wim Declercq. 2018. “Keratinocyte-Specific Ablation of RIPK4 Allows Epidermal Cornification but Impairs Skin Barrier Formation.” JOURNAL OF INVESTIGATIVE DERMATOLOGY 138 (6): 1268–1278. doi:10.1016/j.jid.2017.12.031.
Vancouver
1.
Urwyler C, Tanghe G, Leurs K, Gilbert B, De Rycke R, De Bruyne M, et al. Keratinocyte-Specific Ablation of RIPK4 Allows Epidermal Cornification but Impairs Skin Barrier Formation. JOURNAL OF INVESTIGATIVE DERMATOLOGY. 2018;138(6):1268–78.
IEEE
[1]
C. Urwyler et al., “Keratinocyte-Specific Ablation of RIPK4 Allows Epidermal Cornification but Impairs Skin Barrier Formation,” JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 138, no. 6, pp. 1268–1278, 2018.
@article{8564918,
  abstract     = {{In humans, receptor-interacting protein kinase 4 (RIPK4) mutations can lead to the autosomal recessive Bartsocas-Papas and popliteal pterygium syndromes, which are characterized by severe skin defects, pterygia, as well as clefting. We show here that the epithelial fusions observed in RIPK4 full knockout (KO) mice are E-cadherin dependent, as keratinocyte-specific deletion of E-cadherin in RIPK4 full KO mice rescued the tail-to-body fusion and fusion of oral epithelia. To elucidate RIPK4 function in epidermal differentiation and development, we generated epidermis-specific RIPK4 KO mice (RIPK4 EKO). In contrast to RIPK4 full KO epidermis, RIPK4 EKO epidermis was normally stratified and the outside-in skin barrier in RIPK4 EKO mice was largely intact at the trunk, in contrast to the skin covering the head and the outer end of the extremities. However, RIPK4 EKO mice die shortly after birth due to excessive water loss because of loss of tight junction protein claudin-1 localization at the cell membrane, which results in tight junction leakiness. In contrast, mice with keratinocyte-specific RIPK4 deletion during adult life remain viable. Furthermore, our data indicate that epidermis-specific deletion of RIPK4 results in delayed keratinization and stratum corneum maturation and altered lipid organization and is thus indispensable during embryonic development for the formation of a functional inside-out epidermal barrier.}},
  author       = {{Urwyler, Corinne and Tanghe, Giel and Leurs, Kirsten and Gilbert, Barbara and De Rycke, Riet and De Bruyne, Michiel and Lippens, Saskia and Bartunkova, Sona and De Groote, Philippe and Niessen, Carien and Haftek, Marek and Vandenabeele, Peter and Declercq, Wim}},
  issn         = {{0022-202X}},
  journal      = {{JOURNAL OF INVESTIGATIVE DERMATOLOGY}},
  keywords     = {{BARTSOCAS-PAPAS SYNDROME,KAPPA-B ACTIVATION,STRATUM-CORNEUM,TIGHT,JUNCTIONS,PROTEIN-KINASE,CORNIFIED ENVELOPE,MICE,DIFFERENTIATION,DEFICIENT,GLUCOSYLCERAMIDES}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1268--1278}},
  publisher    = {{Elsevier Science Inc}},
  title        = {{Keratinocyte-Specific Ablation of RIPK4 Allows Epidermal Cornification but Impairs Skin Barrier Formation}},
  url          = {{http://doi.org/10.1016/j.jid.2017.12.031}},
  volume       = {{138}},
  year         = {{2018}},
}
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