Wnt-PLC-IP3-Connexin-Ca2+ axis maintains ependymal motile cilia in zebrafish spinal cord

Jun Zhang; Gopalakrishnan Chandrasekaran; Wenting Li; Dong Young Kim; In Young Jeong; So Hyun Lee; Ting Liang; Jin Young Bae; Isaac Choi; Hyuno Kang; Jin Soo Maeng; Myeong Kyu Kim; Taewon Lee; Seung Woo Park; Min Jung Kim; Hyung Seok Kim; Hyunju Ro; Yong Chul Bae; Hae Chul Park; Eun Young Choi; Seok Yong Choi

doi:10.1038/s41467-020-15248-2

Wnt-PLC-IP₃-Connexin-Ca²⁺ axis maintains ependymal motile cilia in zebrafish spinal cord

Jun Zhang, Gopalakrishnan Chandrasekaran, Wenting Li, Dong Young Kim, In Young Jeong, So Hyun Lee, Ting Liang, Jin Young Bae, Isaac Choi, Hyuno Kang, Jin Soo Maeng, Myeong Kyu Kim, Taewon Lee, Seung Woo Park, Min Jung Kim, Hyung Seok Kim, Hyunju Ro, Yong Chul Bae, Hae Chul Park, Eun Young ChoiSeok Yong Choi

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plcδ3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca²⁺ wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy.

Original language	English
Article number	1860
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15248-2
Publication status	Published - 2020 Dec 1

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/s41467-020-15248-2

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Zhang, J., Chandrasekaran, G., Li, W., Kim, D. Y., Jeong, I. Y., Lee, S. H., Liang, T., Bae, J. Y., Choi, I., Kang, H., Maeng, J. S., Kim, M. K., Lee, T., Park, S. W., Kim, M. J., Kim, H. S., Ro, H., Bae, Y. C., Park, H. C., ... Choi, S. Y. (2020). Wnt-PLC-IP₃-Connexin-Ca²⁺ axis maintains ependymal motile cilia in zebrafish spinal cord. Nature communications, 11(1), Article 1860. https://doi.org/10.1038/s41467-020-15248-2

Zhang, J, Chandrasekaran, G, Li, W, Kim, DY, Jeong, IY, Lee, SH, Liang, T, Bae, JY, Choi, I, Kang, H, Maeng, JS, Kim, MK, Lee, T, Park, SW, Kim, MJ, Kim, HS, Ro, H, Bae, YC, Park, HC, Choi, EY & Choi, SY 2020, 'Wnt-PLC-IP₃-Connexin-Ca²⁺ axis maintains ependymal motile cilia in zebrafish spinal cord', Nature communications, vol. 11, no. 1, 1860. https://doi.org/10.1038/s41467-020-15248-2

@article{21a9183439df464c994bd14949f637df,

title = "Wnt-PLC-IP3-Connexin-Ca2+ axis maintains ependymal motile cilia in zebrafish spinal cord",

abstract = "Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plcδ3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca2+ wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy.",

author = "Jun Zhang and Gopalakrishnan Chandrasekaran and Wenting Li and Kim, {Dong Young} and Jeong, {In Young} and Lee, {So Hyun} and Ting Liang and Bae, {Jin Young} and Isaac Choi and Hyuno Kang and Maeng, {Jin Soo} and Kim, {Myeong Kyu} and Taewon Lee and Park, {Seung Woo} and Kim, {Min Jung} and Kim, {Hyung Seok} and Hyunju Ro and Bae, {Yong Chul} and Park, {Hae Chul} and Choi, {Eun Young} and Choi, {Seok Yong}",

note = "Funding Information: The authors thank Myung-Kwan Han for mouse Cx43 cDNA, Robert Kelsh for fzd3, fzd4, fzd6 and fzd8a plasmids, Vladimir Korzh for fzd7b plasmid, Ichiro Matsumoto for plcβ2 plasmid, Brian Ciruna for p5E-foxJ1aP and Tg(bactin2:Arl13b-GFP), Zebrafish International Resource Center for Tg(hsp70l:dkk1b-GFP), Hyuk Wan Ko for anti-ARL13B antibody, Jeffrey Essner for zebrafish cx43.4 plasmid, Eun Jin Kim for zebrafish TEM, Nan-Hee Choi and Do Won Jang for technical assistance, Hueng-Sik Choi, Richard Dorsky, Masahiko Hibi, Sudipto Roy and Masakatsu Watanabe for critical discussions, Tae-Lin Huh, Joon Haeng Rhee and Hiroki Teraoka for support, and Suk-Won Jin, Jeong-Soo Lee, and Ji Eun Lee for critical read of the manuscript. This work was supported by Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (2015-R1D1A1A01056877), and the NRF grant funded by the Ministry of Science and ICT (MSIT) of the government of Korea (2016R1E1A1A01943329). J.Z., G.C., and T.Liang. thank the Enam Fellowship Foundation for a graduate fellowship. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-15248-2",

language = "English",

volume = "11",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Wnt-PLC-IP3-Connexin-Ca2+ axis maintains ependymal motile cilia in zebrafish spinal cord

AU - Zhang, Jun

AU - Chandrasekaran, Gopalakrishnan

AU - Li, Wenting

AU - Kim, Dong Young

AU - Jeong, In Young

AU - Lee, So Hyun

AU - Liang, Ting

AU - Bae, Jin Young

AU - Choi, Isaac

AU - Kang, Hyuno

AU - Maeng, Jin Soo

AU - Kim, Myeong Kyu

AU - Lee, Taewon

AU - Park, Seung Woo

AU - Kim, Min Jung

AU - Kim, Hyung Seok

AU - Ro, Hyunju

AU - Bae, Yong Chul

AU - Park, Hae Chul

AU - Choi, Eun Young

AU - Choi, Seok Yong

N1 - Funding Information: The authors thank Myung-Kwan Han for mouse Cx43 cDNA, Robert Kelsh for fzd3, fzd4, fzd6 and fzd8a plasmids, Vladimir Korzh for fzd7b plasmid, Ichiro Matsumoto for plcβ2 plasmid, Brian Ciruna for p5E-foxJ1aP and Tg(bactin2:Arl13b-GFP), Zebrafish International Resource Center for Tg(hsp70l:dkk1b-GFP), Hyuk Wan Ko for anti-ARL13B antibody, Jeffrey Essner for zebrafish cx43.4 plasmid, Eun Jin Kim for zebrafish TEM, Nan-Hee Choi and Do Won Jang for technical assistance, Hueng-Sik Choi, Richard Dorsky, Masahiko Hibi, Sudipto Roy and Masakatsu Watanabe for critical discussions, Tae-Lin Huh, Joon Haeng Rhee and Hiroki Teraoka for support, and Suk-Won Jin, Jeong-Soo Lee, and Ji Eun Lee for critical read of the manuscript. This work was supported by Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (2015-R1D1A1A01056877), and the NRF grant funded by the Ministry of Science and ICT (MSIT) of the government of Korea (2016R1E1A1A01943329). J.Z., G.C., and T.Liang. thank the Enam Fellowship Foundation for a graduate fellowship. Publisher Copyright: © 2020, The Author(s).

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plcδ3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca2+ wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy.

AB - Ependymal cells (ECs) are multiciliated neuroepithelial cells that line the ventricles of the brain and the central canal of the spinal cord (SC). How ependymal motile cilia are maintained remains largely unexplored. Here we show that zebrafish embryos deficient in Wnt signaling have defective motile cilia, yet harbor intact basal bodies. With respect to maintenance of ependymal motile cilia, plcδ3a is a target gene of Wnt signaling. Lack of Connexin43 (Cx43), especially its channel function, decreases motile cilia and intercellular Ca2+ wave (ICW) propagation. Genetic ablation of cx43 in zebrafish and mice diminished motile cilia. Finally, Cx43 is also expressed in ECs of the human SC. Taken together, our findings indicate that gap junction mediated ICWs play an important role in the maintenance of ependymal motile cilia, and suggest that the enhancement of functional gap junctions by pharmacological or genetic manipulations may be adopted to ameliorate motile ciliopathy.

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U2 - 10.1038/s41467-020-15248-2

DO - 10.1038/s41467-020-15248-2

M3 - Article

C2 - 32312952

AN - SCOPUS:85083771490

SN - 2041-1723

VL - 11

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 1860

ER -

Wnt-PLC-IP₃-Connexin-Ca²⁺ axis maintains ependymal motile cilia in zebrafish spinal cord

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