TY - JOUR
T1 - Calcium oscillations coordinate feather mesenchymal cell movement by SHH dependent modulation of gap junction networks
AU - Li, Ang
AU - Cho, Jung Hwa
AU - Reid, Brian
AU - Tseng, Chun Chih
AU - He, Lian
AU - Tan, Peng
AU - Yeh, Chao Yuan
AU - Wu, Ping
AU - Li, Yuwei
AU - Widelitz, Randall B.
AU - Zhou, Yubin
AU - Zhao, Min
AU - Chow, Robert H.
AU - Chuong, Cheng Ming
PY - 2018/12/1
Y1 - 2018/12/1
N2 -
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 Ca
2+
channels (VGCCs), Connexin-43 based gap junctions, and Ca
2+
release activated Ca
2+
(CRAC) channels. 4-Dimensional Ca
2+
imaging reveals that the Sonic hedgehog-responsive mesenchymal cells display synchronized Ca
2+
oscillations, which expand progressively in area during feather elongation. Inhibiting VGCCs, gap junctions, or Sonic hedgehog signaling alters the mesenchymal Ca
2+
landscape, cell movement patterns and feather bud elongation. Ca
2+
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 Ca
2+
profile among cells, thereby coordinating cell movement patterns.
AB -
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 Ca
2+
channels (VGCCs), Connexin-43 based gap junctions, and Ca
2+
release activated Ca
2+
(CRAC) channels. 4-Dimensional Ca
2+
imaging reveals that the Sonic hedgehog-responsive mesenchymal cells display synchronized Ca
2+
oscillations, which expand progressively in area during feather elongation. Inhibiting VGCCs, gap junctions, or Sonic hedgehog signaling alters the mesenchymal Ca
2+
landscape, cell movement patterns and feather bud elongation. Ca
2+
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 Ca
2+
profile among cells, thereby coordinating cell movement patterns.
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U2 - 10.1038/s41467-018-07661-5
DO - 10.1038/s41467-018-07661-5
M3 - Article
C2 - 30560870
AN - SCOPUS:85058748970
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 5377
ER -