Voltage-dependent Ca2+ channels promote branching morphogenesis of salivary glands by patterning differential growth

Scientific Reports
J M KimK Park

Abstract

Branching morphogenesis is a crucial part of early developmental processes in diverse organs, but the detailed mechanism of this morphogenic event remains to be elucidated. Here we introduce an unknown mechanism leading to branching morphogenesis using mouse embryonic organotypic cultures with time-lapse live imaging. We found spatially expressed L-type voltage-dependent Ca2+ channels (VDCCs) in the peripheral layers of developing epithelial buds and identified the VDCCs as a core signaling mediator for patterning branching architecture. In this process, differential growth in peripheral layers by VDCC-induced ERK activity promoted cleft formation through an epithelial buckling-folding mechanism. Our findings reveal an unexpected role of VDCCs in developmental processes, and address a fundamental question regarding the initial process of branching morphogenesis.

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Citations

Jan 14, 2021·International Journal of Molecular Sciences·Junchul KimKyungpyo Park

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Methods Mentioned

BETA
biosensor
PCR
nuclear translocation
fluorescence resonance
X-ray
biosensors
nucleotide exchange
FRET
transfection
electrophoresis

Software Mentioned

Fiji
Analysis ToolPak - VBA
Excel

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