A sex chromosome drives the emergence of vocal learning following hormonal manipulation in female zebra finches

Abstract

Zebra finches are sexually dimorphic vocal learners. Males learn to sing by imitating mature conspecifics, but females do not. The lack of vocal learning in females is associated with anatomical differences in the neural circuits responsible for vocal learning, including the atrophy of several brain regions during development1. However, this atrophy can be prevented and song learning retained in females after pharmacological estrogen treatment2–4. Little is known about the genetic machinery controlling this sex and estrogen responsive song system development. To screen for drivers, we performed an unbiased analysis of transcriptomes from song control nuclei and surrounding motor regions in zebra finches of either sex treated with 17-β-estradiol or vehicle until sacrifice on day 30, when divergence between the sexes is anatomically apparent. Utilizing the newly assembled autosomes and sex chromosomes from the zebra finch Vertebrate Genomes Project assemblies5, we identified correlated gene modules that were associated to song nuclei in a sex and estradiol dependent manner. Female estradiol treated HVC, in the vocal learning circuit, acquired the smallest of the modular specializations observed in male HVC. This module was enriched for genes governing anatomical development, and it’s specilization was dispraportionately influenced by the expression of Z sex chromosome transcripts in HVC. We propose that vocal learning may be prevented in female zebra finches via the suppression of an estrogen inducible Z chromosome cis-acting regulatory element.