Decrease in excitatory neurons, astrocytes and proliferating progenitors in the cerebral cortex of mice lacking exon...

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• FGF2 gene expression in embryonic brain and adult glial cells.
• Previous studies suggested FGF2's role in embryonic neural progenitor proliferation using exon 1 knockouts.
• Alternative splicing of Fgf2 transcripts may have confounded earlier knockout results.

Purpose of the Study:

• To generate and characterize a new Fgf2 knockout mouse model.
• To investigate the role of Fgf2 exon 3, essential for receptor binding, in neural development.
• To compare the phenotype of exon 3 knockouts with existing exon 1 knockout models.

Main Methods:

• Generated Fgf2 knockout mice lacking exon 3 using a transcriptional STOP cassette.
• Analyzed the adult neocortex phenotype, including neuron and astrocyte density.
• Assessed the proliferation of adult cortical precursors.

Main Results:

• Fgf2 exon 3 knockout mice exhibited a phenotype identical to exon 1 knockouts.
• Observed decreased density and number of cortical excitatory neurons and astrocytes.
• Demonstrated reduced proliferation of adult cortical precursor cells.

Conclusions:

• Fgf2 knockout models lacking exon 1 or exon 3 show similar phenotypes.
• FGF2 is essential for cortical cell genesis during embryonic development and adulthood.
• FGF2 is required for maintaining the adult cortical progenitor cell pool.