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Related Experiment Videos

Dose-dependent functions of Fgf8 in regulating telencephalic patterning centers.

Elaine E Storm1, Sonia Garel, Ugo Borello

  • 1Department of Anatomy, University of California, San Francisco, CA 94143-2711, USA.

Development (Cambridge, England)
|April 15, 2006
PubMed
Summary

Fibroblast growth factor 8 (FGF8) signaling is crucial for telencephalon development in mouse embryos. Reduced FGF8 signaling leads to smaller brains, altered gene expression, and abnormal patterning, impacting brain structure formation.

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Area of Science:

  • Developmental biology
  • Neuroscience
  • Genetics

Background:

  • Fibroblast growth factor 8 (FGF8) is a key signaling molecule in embryonic development.
  • Proper telencephalon development is essential for brain function.
  • FGF8 mutations can lead to severe developmental defects.

Purpose of the Study:

  • To investigate the role of FGF8 in telencephalon patterning and development.
  • To elucidate the molecular mechanisms underlying FGF8-mediated brain development.
  • To understand the consequences of altered FGF8 signaling on gene expression and cellular processes.

Main Methods:

  • Utilized mouse models with hypomorphic and conditional null Fgf8 mutations.
  • Analyzed telencephalon size, patterning, cell proliferation, and cell death.

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  • Examined the expression patterns of key developmental genes (Foxg1, Bmp4, Wnt8b, Nkx2.1, Shh, Msx1).

    • Main Results:

    • Fgf8 mutations resulted in smaller, abnormally patterned telencephalons.
    • Hypoplasia was linked to decreased Foxg1 expression, reduced proliferation, and increased cell death.
    • Altered expression of Bmp4, Wnt8b, Nkx2.1, and Shh was observed.
    • Nonlinear Fgf8 gene dose effects correlated with holoprosencephaly and altered transcription factor expression.

    Conclusions:

    • FGF8 signaling coordinates multiple patterning centers during telencephalon development.
    • Modulating FGF8 signaling strength profoundly impacts telencephalic subdivision size and characteristics.
    • FGF8 is critical for regulating gene expression networks essential for neocortical patterning.