Abstract

To execute the intricate process of development, cells coordinate across tissues and organs to determine where each cell divides and differentiates. This coordination requires complex communication between cells. Growing evidence suggests that bioelectrical signals controlled via ion channels contribute to cell communication during development. Ion channels collectively regulate the transmembrane potential of cells, and their function plays a conserved role in the development of organisms from flies to humans. Spontaneous calcium oscillations can be found in nearly every cell type and tissue, and disruption of these oscillations leads to defects in development. However, the mechanism by which bioelectricity regulates development is still unclear. Ion channels play essential roles in the processes of cell death, proliferation, migration, and in each of the major canonical developmental signaling pathways. Previous reviews focus on evidence for one potential mechanism by which bioelectricity affects morphogenesis, but there is evidence that supports multiple different mechanisms which are not mutually exclusive. Evidence supports bioelectricity contributing to development through multiple different mechanisms. Here, we review evidence for the importance of bioelectricity in morphogenesis and provide a comprehensive review of the evidence for several potential mechanisms by which ion channels may act in developmental processes.

Highlights

  • The process by which a single fertilized egg develops into a multicellular organism is a remarkable feat of biology

  • This increase in Wnt signaling upon CTFR disruption may be one of reasons why cystic fibrosis is associated with abnormal lung development and increased risk of gastrointestinal cancer (Neglia et al, 1995; Larson and Cohen, 2005)

  • The hedgehog signaling pathway family members, including sonic hedgehog (Shh), desert hedgehog (Dhh), and Indian hedgehog (Ihh) all play an essential role in embryonic patterning and development (Choy and Cheng, 2012)

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Summary

Laura Faith George and Emily Anne Bates *

To execute the intricate process of development, cells coordinate across tissues and organs to determine where each cell divides and differentiates. This coordination requires complex communication between cells. Growing evidence suggests that bioelectrical signals controlled via ion channels contribute to cell communication during development. Ion channels collectively regulate the transmembrane potential of cells, and their function plays a conserved role in the development of organisms from flies to humans. We review evidence for the importance of bioelectricity in morphogenesis and provide a comprehensive review of the evidence for several potential mechanisms by which ion channels may act in developmental processes

INTRODUCTION
OVERVIEW OF BIOELECTRICITY IN DEVELOPMENT
ION CHANNEL SIGNALING IN HUMAN DEVELOPMENT
CONSERVATION OF ION CHANNEL ROLES IN MORPHOGENESIS
CELL DEATH PATHWAYS
PROLIFERATION AND CELL CYCLE REGULATION
CELL POLARITY AND MIGRATION
REGULATION OF CANONICAL DEVELOPMENTAL SIGNALING PATHWAYS
Bone Morphogenetic Protein Pathway
Notch Pathway
Wnt Pathway
Hedgehog Pathway
DIRECT REGULATION OF TRANSCRIPTION
Remaining Questions
Potential Barriers
CONCLUDING REMARKS
Full Text
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