Sex chromosome gene expression associated with vocal learning following hormonal manipulation in female zebra finches

Zebra finches are sexually dimorphic vocal learners. Males learn to sing by imitating mature conspecifics, but females do not. Absence of song in females is associated with atrophy and apparent repression of several vocal learning brain regions during development. However, atrophy can be prevented and vocal learning retained in females when given early pharmacological estrogen treatment. To screen for drivers, we performed an unbiased transcriptomic analysis of song learning nuclei and surrounding regions from either sex, treated with vehicle or estrogen until 30 days old when divergence between the sexes becomes anatomically apparent. Analyses of transcriptomes by RNA sequencing identified song nuclei expressed gene modules associated with sex and estrogen manipulation. Female HVC and Area X gene modules were specialized by supplemental estrogen, exhibiting a subset of the transcriptomic specializations observed in males. Female RA and LMAN specialized modules were less dependent on estrogen. The estrogen-induced gene modules in females were enriched for anatomical development functions and strongly correlated to the expression of several Z sex chromosome genes. We present a hypothesis linking loss and de-repression of vocal learning in females, estrogen, and sex chromosomes gene expression.