Foxn1 is not essential for T-cell development in teleosts

Area of Science:

• Developmental biology
• Immunology
• Evolutionary biology

Background:

• T-cell development in mammals critically relies on the Foxn1 transcription factor within the thymic epithelium.
• Mutations in Foxn1 lead to severe T-cell deficiency and fatal immunodeficiency in vertebrates.

Purpose of the Study:

• To investigate T-cell development in teleosts that lack a functional foxn1 gene.
• To understand the evolutionary role of Foxn1 in T-cell development across different vertebrate lineages.

Main Methods:

• Analysis of zebrafish with a foxn1 gene deletion.
• Genomic examination of deep-sea anglerfishes for foxn1 gene status.
• Assessment of T-cell lineage markers in teleost species.

Main Results:

• Zebrafish lacking functional foxn1 maintain reduced but robust thymic lymphopoietic activity.
• Loss or pseudogenization of foxn1 in anglerfish does not affect T-cell lineage markers.
• Teleost thymus supports foxn1-independent lymphopoiesis, likely via Foxn4.

Conclusions:

• Teleost thymopoiesis is not solely dependent on Foxn1, unlike in mammals.
• Early vertebrate thymopoiesis exhibited functional redundancy, with Foxn4 potentially compensating for Foxn1.
• Mammalian T-cell development evolved a unique dependence on the FOXN1 transcription factor.