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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

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Cell cycle-related kinase regulates mammalian eye development through positive and negative regulation of the

Floria I Lupu1, Jacob B Burnett1, Jonathan T Eggenschwiler1

  • 1Department of Genetics, University of Georgia, Athens, GA 30602, USA.

Developmental Biology
|November 23, 2017
PubMed

Insights

Cell cycle-related kinase (CCRK) is crucial for mouse eye development, regulating Hedgehog (Hh) signaling. Its absence causes severe patterning defects and altered Hh pathway activity, impacting eye morphogenesis.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Cell cycle-related kinase (CCRK) is a conserved regulator of ciliogenesis.
  • Loss of CCRK in mice results in various developmental defects, including microphthalmia.

Purpose of the Study:

  • Investigate the role of CCRK in mouse eye development.
  • Elucidate the mechanisms by which CCRK influences eye patterning and morphogenesis.

Main Methods:

  • Analysis of Ccrk mutant mice.
  • Genetic manipulation of Hedgehog (Hh) pathway components (GLI2, GLI3) in Ccrk mutants.
  • Assessment of eye patterning and RPE/NR territory.

Main Results:

  • Ccrk mutants exhibit optic stalk/cup patterning defects and RPE expansion into neural retina (NR).
  • These defects correlate with bimodal changes in Hh pathway activity (loss of proximal, gain of distal responses).
  • Genetic disruption of GLI2 or GLI3 in Ccrk mutants reveals distinct roles in eye patterning and morphogenesis.

Conclusions:

  • CCRK plays a dual role in regulating the Hh pathway during eye development.
  • CCRK is essential for proper eye patterning and morphogenesis through modulation of Hh signaling.
Keywords:
CiliogenesisGLI2GLI3Neural retinaOptic stalkRetinal pigment epithelium

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