Journal Article

Functional Equivalence of the SOX2 and SOX3 Transcription Factors in the Developing Mouse Brain and Testes

McAninch, Dale, Thomas, Paul, Adikusuma, Fatwa, Pederick, Daniel, Hughes, James

2017

Overview

Gene duplication provides spare genetic material that evolution can craft into new functions. Sox2 and Sox3 are evolutionarily related genes with overlapping and unique sites of expression during embryogenesis. It is currently unclear whether SOX2 and SOX3 have identical or different functions. Here, we use CRISPR/Cas9-assisted mutagenesis to perform a gene-swap, replacing the Sox3 ORF with the Sox2 ORF to investigate their functional equivalence in the brain and testes. We show that increased expression of SOX2 can functionally replace SOX3 in the development of the infundibular recess/ventral diencephalon, and largely rescues pituitary gland defects that occur in Sox3 null mice. We also show that ectopic expression of SOX2 in the testes functionally rescues the spermatogenic defect of Sox3 null mice, and restores gene expression to near normal levels. Together, these in vivo data provide strong evidence that SOX2 and SOX3 proteins are functionally equivalent.

• Publisher: Genetics Society of America
• Subject: Animals / Biological evolution / Brain / Brain - growth & development / Brain - metabolism / CRISPR / CRISPR-Cas Systems / Defects / Diencephalon / Ectopic expression / Embryogenesis / Embryonic growth stage / Equivalence / Evolution / Female / Gene duplication / Gene expression / Genetic engineering / Genetics / Genomes / Investigations / Male / Mice / Mice, Inbred C57BL / Mutagenesis / Mutation / Open Reading Frames / Pituitary / Pituitary gland / Proteins / Rodents / SOXB1 Transcription Factors - genetics / SOXB1 Transcription Factors - metabolism / Testes / Testis - growth & development / Testis - metabolism / Transcription factors