Formation of regulator/target gene relationships during evolution

Area of Science:

• Evolutionary developmental biology
• Genetics
• Molecular evolution

Background:

• The Foxn1 transcription factor is essential for mammalian hair follicle development.
• Hair follicles are evolutionarily novel structures unique to mammals.
• Foxn1-like genes are conserved across chordates.

Purpose of the Study:

• To investigate the functional conservation of Foxn1-like genes throughout vertebrate evolution.
• To understand the molecular basis for changes in Foxn1 function during evolution.
• To explore the evolution of gene regulation in novel organ development.

Main Methods:

• Comparative gene expression analysis
• Functional assays of transcription factor activity
• Sequence analysis of Foxn1-like genes from different species (fish, mouse, Branchiostoma lanceolatum)

Main Results:

• Fish and mouse Foxn1-like genes are functionally equivalent in activating hair keratin gene expression.
• The Foxn1-like gene from Branchiostoma lanceolatum is inactive in this assay.
• Functional inactivation in Branchiostoma is linked to changes in the N-terminal region of the protein, outside the DNA binding and activation domains.

Conclusions:

• Foxn1 function in hair keratin gene regulation has been highly conserved throughout vertebrate evolution.
• Evolutionarily novel regulatory relationships can arise from changes in cis-regulatory elements without concurrent changes in the transcription factor protein.
• The N-terminal region of Foxn1 plays a role in its regulatory activity, with evolutionary changes in this region affecting function.