Gli3 is required for Emx gene expression during dorsal telencephalon development

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• The dentate gyrus and hippocampus are vital for spatial learning, memory, and emotional behavior.
• Molecular mechanisms of dorsal telencephalon development, including the hippocampus, are not fully understood.
• Emx genes were previously the only known requirement for dorsal telencephalon development.

Purpose of the Study:

• To investigate the role of the Gli3 gene in forebrain development.
• To identify molecular regulators of dorsal telencephalon and hippocampus formation.
• To elucidate the genetic cascade controlling dorsal telencephalic development.

Main Methods:

• Analysis of the extra toes (Xt(J)) mouse mutant with a Gli3 null mutation.
• Examination of embryonic forebrain development, including the neocortex and hippocampus.
• Molecular analysis of gene expression patterns (Emx1, Emx2, Fgf8, Bmp4, Shh).

Main Results:

• Gli3 mutation (Xt(J)/Xt(J)) leads to failure in establishing the dorsal di-telencephalic junction.
• Severe neocortex size reduction and absence of the hippocampus and choroid plexus in Xt(J)/Xt(J) mice.
• Altered expression of Emx1, Emx2, Fgf8, and Bmp4, but not Shh, in the mutant forebrain.

Conclusions:

• Gli3 is a key regulator of dorsal telencephalon development.
• Gli3 acts upstream of Emx genes in the genetic pathway for dorsal telencephalon formation.
• The Gli3 gene is essential for the proper invagination of the medial telencephalon during embryonic development.