Calcium oscillations coordinate feather mesenchymal cell movement by SHH dependent modulation of gap junction networks

Ang Li; Jung-Hwa Cho; Brian Reid; Chun-Chih Tseng; Lian He; Peng Tan; Chao-Yuan Yeh; Ping Wu; Yuwei Li; Randall B Widelitz; Yubin Zhou; Min Zhao; Robert H Chow; Cheng-Ming Chuong

doi:10.1038/s41467-018-07661-5

Calcium oscillations coordinate feather mesenchymal cell movement by SHH dependent modulation of gap junction networks

Nat Commun. 2018 Dec 18;9(1):5377. doi: 10.1038/s41467-018-07661-5.

Authors

Ang Li^{1

2}, Jung-Hwa Cho^{3

4}, Brian Reid⁵, Chun-Chih Tseng^{1

6}, Lian He⁷, Peng Tan⁷, Chao-Yuan Yeh^{1

8}, Ping Wu¹, Yuwei Li⁹, Randall B Widelitz¹, Yubin Zhou⁷, Min Zhao⁵, Robert H Chow¹⁰, Cheng-Ming Chuong^{11

12}

Affiliations

¹ Dept. of Pathology, USC Keck School of Medicine, Los Angeles, CA, 90033, USA.
² Dept. of Kinesiology, University of Texas at Arlington, Arlington, TX, 76019, USA.
³ Dept. of Physiology & Biophysics, USC Keck School of Medicine, Los Angeles, CA, 90033, USA.
⁴ National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, 20824, USA.
⁵ Dept. of Dermatology, UC Davis School of Medicine, Sacramento, CA, 95817, USA.
⁶ Dept. of Biochemistry & Molecular Biology, USC Keck School of Medicine, Los Angeles, CA, 90033, USA.
⁷ Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX, 77030, USA.
⁸ Integrative Stem Cell Center, China Medical University Hospital, 404, Taichung, Taiwan.
⁹ Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
¹⁰ Dept. of Physiology & Biophysics, USC Keck School of Medicine, Los Angeles, CA, 90033, USA. rchow@med.usc.edu.
¹¹ Dept. of Pathology, USC Keck School of Medicine, Los Angeles, CA, 90033, USA. cmchuong@med.usc.edu.
¹² Integrative Stem Cell Center, China Medical University Hospital, 404, Taichung, Taiwan. cmchuong@med.usc.edu.

Abstract

Collective cell migration mediates multiple tissue morphogenesis processes. Yet how multi-dimensional mesenchymal cell movements are coordinated remains mostly unknown. Here we report that coordinated mesenchymal cell migration during chicken feather elongation is accompanied by dynamic changes of bioelectric currents. Transcriptome profiling and functional assays implicate contributions from functional voltage-gated Ca²⁺ channels (VGCCs), Connexin-43 based gap junctions, and Ca²⁺ release activated Ca²⁺ (CRAC) channels. 4-Dimensional Ca²⁺ imaging reveals that the Sonic hedgehog-responsive mesenchymal cells display synchronized Ca²⁺ oscillations, which expand progressively in area during feather elongation. Inhibiting VGCCs, gap junctions, or Sonic hedgehog signaling alters the mesenchymal Ca²⁺ landscape, cell movement patterns and feather bud elongation. Ca²⁺ oscillations induced by cyclic activation of opto-cCRAC channels enhance feather bud elongation. Functional disruption experiments and promoter analysis implicate synergistic Hedgehog and WNT/β-Catenin signaling in activating Connexin-43 expression, establishing gap junction networks synchronizing the Ca²⁺ profile among cells, thereby coordinating cell movement patterns.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium Signaling / physiology*
Cell Movement / physiology*
Cells, Cultured
Chickens
Connexin 43 / genetics
Connexin 43 / metabolism*
Embryo, Nonmammalian
Feathers / cytology
Feathers / growth & development*
Gap Junctions / metabolism
Hedgehog Proteins / metabolism*
Mesoderm / cytology
Mesoderm / physiology
Morphogenesis / physiology
Promoter Regions, Genetic
Skin / cytology
Wnt Signaling Pathway / physiology

Substances

Connexin 43
Hedgehog Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding