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A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
12:27

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors

Published on: June 8, 2022

Sphingosine 1-phosphate receptors are essential mediators of eyelid closure during embryonic development

Deron R Herr1, Chang-Wook Lee, Wei Wang

  • 1From the Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037 and.

The Journal of Biological Chemistry
|September 5, 2013
PubMed

Insights

Sphingosine 1-phosphate (S1P) receptors S1P2 and S1P3 are crucial for mammalian eyelid closure. Double-null mouse embryos lacking both receptors exhibit delayed epithelial extension, resulting in an "eyes open at birth" phenotype.

Area of Science:

  • Developmental Biology
  • Molecular Signaling
  • Ophthalmology

Background:

  • Mammalian eyelid development involves epithelial expansion, fusion, and splitting.
  • Molecular signaling pathways are critical for proper eyelid formation.
  • The role of sphingosine 1-phosphate (S1P) signaling in eyelid development was previously unknown.

Purpose of the Study:

  • To investigate the involvement of S1P receptors in mammalian eyelid development.
  • To determine the specific S1P receptors essential for eyelid closure.
  • To elucidate the molecular mechanisms underlying S1P-mediated eyelid development.

Main Methods:

  • Generation of knockout mouse models for S1P2 and S1P3 receptors.
  • Phenotypic analysis of eyelid development in wild-type and mutant embryos.
  • Assessment of epithelial sheet extension and cell signaling pathways.

Main Results:

  • Deletion of individual S1P2 or S1P3 genes had no effect on eyelid development.
  • Double-null embryos lacking both S1P2 and S1P3 receptors displayed an "eyes open at birth" phenotype.
  • These double-null embryos showed delayed epithelial sheet extension during eyelid closure.
  • S1P2 and S1P3 receptors are expressed in the advancing epithelial sheet during development.
  • Fibroblasts from double-null embryos exhibited impaired epidermal growth factor (EGF) signaling.

Conclusions:

  • Sphingosine 1-phosphate receptors S1P2 and S1P3 are collectively essential for murine eyelid closure.
  • These receptors appear to modulate epidermal growth factor signaling during eyelid development.
  • The findings reveal a novel role for S1P signaling in the complex process of eyelid formation.
Keywords:
DevelopmentERKEpidermal Growth Factor (EGF)EyeG Protein-coupled Receptors (GPCRs)Gene KnockoutMAP Kinases (MAPKs)MouseSphingolipidSphingosine 1-Phosphate

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