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Theranostics 2019; 9(17):5065-5084. doi:10.7150/thno.34014 This issue Cite

Research Paper

Cdc42 Deficiency Leads To Epidermal Barrier Dysfunction by Regulating Intercellular Junctions and Keratinization of Epidermal Cells during Mouse Skin Development

Min Zhang1*, Xueer Wang1*, Fukun Guo3, Qin Jia1, Nuyun Liu4, Yinghua Chen1, Yuan Yan1, Mianbo Huang1, Huiyi Tang1, Ying Deng1, Simin Huang1, Zhitao Zhou1, Lu Zhang2✉, Lin Zhang1✉

1. Department of Histology and Embryology, Guangdong Provincial Key Laboratory of Tissue Construction and Detection, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People's Republic of China
2. Guangdong Provincial Key Laboratory of Proteomics, Key Laboratory of Mental Health of the Ministry of Education, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People's Republic of China
3. Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, Cincinnati, Ohio, USA
4. Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou, 510515, China.
*These authors contributed equally.

✉ Corresponding authors: Dr. Lin Zhang or Dr. Lu Zhang, Southern Medical University, No. 1023 Sha Tai Road, Baiyun District, Guangzhou 510515, People's Republic of China. E-mail: zlilyzhcom (Lin Zhang), telephone: 8602061648205; e-mail: zlulu70com (Lu Zhang), telephone: 8602061648726. More

Citation:
Zhang M, Wang X, Guo F, Jia Q, Liu N, Chen Y, Yan Y, Huang M, Tang H, Deng Y, Huang S, Zhou Z, Zhang L, Zhang L. Cdc42 Deficiency Leads To Epidermal Barrier Dysfunction by Regulating Intercellular Junctions and Keratinization of Epidermal Cells during Mouse Skin Development. Theranostics 2019; 9(17):5065-5084. doi:10.7150/thno.34014. https://www.thno.org/v09p5065.htm
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Abstract

Graphic abstract

Rationale: Cdc42 is a Rho GTPase that regulates diverse cellular functions. Here, we used genetic techniques to investigate the role of Cdc42 in epidermal development and epidermal barrier formation.

Methods: Keratinocyte-restricted Cdc42 knockout mice were generated with the Cre-LoxP system under the keratin 14 (K14) promoter. The skin and other tissues were collected from mutant and wild-type mice, and their cellular, molecular, morphological, and physiological features were analyzed.

Results: Loss of Cdc42 in the epidermis in vivo resulted in neonatal lethality and impairment of epidermal barrier formation. Cdc42 deficiency led to the loss of epidermal stem cells. The absence of Cdc42 led to increased thickening of the epidermis, which was associated with increased proliferation and reduced apoptosis of keratinocytes. In addition, Cdc42 deficiency damaged tight junctions, adherens junctions and desmosomes. RNA sequencing results showed that the most significantly altered genes were enriched by the terms of “keratinization” and “cornified envelope” (CE). Among the differentially expressed genes in the CE term, several members of the small proline-rich protein (SPRR) family were upregulated. Further study revealed that there may be a Cdc42-SPRR pathway, which may correlate with epidermal barrier function.

Conclusions: Our study indicates that Cdc42 is essential for epidermal development and epidermal barrier formation. Defects in Cdc42-SPRR signaling may be associated with skin barrier dysfunction and a variety of skin diseases.

Keywords: Cdc42, SPRR, epidermal barrier, epidermal development

Citation styles

APA
Zhang, M., Wang, X., Guo, F., Jia, Q., Liu, N., Chen, Y., Yan, Y., Huang, M., Tang, H., Deng, Y., Huang, S., Zhou, Z., Zhang, L., Zhang, L. (2019). Cdc42 Deficiency Leads To Epidermal Barrier Dysfunction by Regulating Intercellular Junctions and Keratinization of Epidermal Cells during Mouse Skin Development. Theranostics, 9(17), 5065-5084. https://doi.org/10.7150/thno.34014.

ACS
Zhang, M.; Wang, X.; Guo, F.; Jia, Q.; Liu, N.; Chen, Y.; Yan, Y.; Huang, M.; Tang, H.; Deng, Y.; Huang, S.; Zhou, Z.; Zhang, L.; Zhang, L. Cdc42 Deficiency Leads To Epidermal Barrier Dysfunction by Regulating Intercellular Junctions and Keratinization of Epidermal Cells during Mouse Skin Development. Theranostics 2019, 9 (17), 5065-5084. DOI: 10.7150/thno.34014.

NLM
Zhang M, Wang X, Guo F, Jia Q, Liu N, Chen Y, Yan Y, Huang M, Tang H, Deng Y, Huang S, Zhou Z, Zhang L, Zhang L. Cdc42 Deficiency Leads To Epidermal Barrier Dysfunction by Regulating Intercellular Junctions and Keratinization of Epidermal Cells during Mouse Skin Development. Theranostics 2019; 9(17):5065-5084. doi:10.7150/thno.34014. https://www.thno.org/v09p5065.htm

CSE
Zhang M, Wang X, Guo F, Jia Q, Liu N, Chen Y, Yan Y, Huang M, Tang H, Deng Y, Huang S, Zhou Z, Zhang L, Zhang L. 2019. Cdc42 Deficiency Leads To Epidermal Barrier Dysfunction by Regulating Intercellular Junctions and Keratinization of Epidermal Cells during Mouse Skin Development. Theranostics. 9(17):5065-5084.

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