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 partial atrophy and apparent repression of several vocal learning brain regions during development. However, atrophy can be pre...

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Main Authors: Matthew Davenport, Ha Na Choe, Hiroaki Matsunami, Erich Jarvis
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2025-06-01
Series:eLife
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Online Access:https://elifesciences.org/articles/89425
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author Matthew Davenport
Ha Na Choe
Hiroaki Matsunami
Erich Jarvis
author_facet Matthew Davenport
Ha Na Choe
Hiroaki Matsunami
Erich Jarvis
author_sort Matthew Davenport
collection DOAJ
description 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 partial 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 candidate drivers of this sexual dimorphism, we performed an unbiased transcriptomic analysis of song learning nuclei specializations relative to the surrounding regions from either sex, treated with vehicle or estrogen until 30 days of age when divergence between the sexes becomes anatomically apparent. Analyses of transcriptomes by RNA sequencing identified song nuclei-specialized gene expressed modules associated with sex and estrogen manipulation. Female HVC and Area X gene modules were specialized by estrogen supplementation, exhibiting a subset of the transcriptomic specializations observed in males. Female robust nucleus of the arcopallium (RA) and lateral magnocellular nucleus of the anterior nidopallium (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 where reduced dosage and expression of these Z chromosome genes suppress the full development of the song system and thus song learning behavior, which is partially rescued by estrogen treatment.
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spelling doaj-art-2caa945cc4954ec7829df38f54d7d31f2025-08-20T03:29:52ZengeLife Sciences Publications LtdeLife2050-084X2025-06-011210.7554/eLife.89425Sex chromosome gene expression associated with vocal learning following hormonal manipulation in female zebra finchesMatthew Davenport0https://orcid.org/0000-0002-5699-6295Ha Na Choe1https://orcid.org/0000-0001-9535-5258Hiroaki Matsunami2https://orcid.org/0000-0002-8850-2608Erich Jarvis3https://orcid.org/0000-0001-8931-5049Laboratory Language Neurogenetics, The Rockefeller University, New York City, United StatesDepartment of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United StatesDepartment of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States; Department of Neurobiology, Duke Institute for Brain Sciences, Duke University School of Medicine, Durham, United StatesLaboratory Language Neurogenetics, The Rockefeller University, New York City, United States; Howard Hughes Medical Institute, Chevy Chase, United StatesZebra 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 partial 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 candidate drivers of this sexual dimorphism, we performed an unbiased transcriptomic analysis of song learning nuclei specializations relative to the surrounding regions from either sex, treated with vehicle or estrogen until 30 days of age when divergence between the sexes becomes anatomically apparent. Analyses of transcriptomes by RNA sequencing identified song nuclei-specialized gene expressed modules associated with sex and estrogen manipulation. Female HVC and Area X gene modules were specialized by estrogen supplementation, exhibiting a subset of the transcriptomic specializations observed in males. Female robust nucleus of the arcopallium (RA) and lateral magnocellular nucleus of the anterior nidopallium (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 where reduced dosage and expression of these Z chromosome genes suppress the full development of the song system and thus song learning behavior, which is partially rescued by estrogen treatment.https://elifesciences.org/articles/89425T. castanotisvocal learningT. guttatasex differencesex chromosomessex hormones
spellingShingle Matthew Davenport
Ha Na Choe
Hiroaki Matsunami
Erich Jarvis
Sex chromosome gene expression associated with vocal learning following hormonal manipulation in female zebra finches
eLife
T. castanotis
vocal learning
T. guttata
sex difference
sex chromosomes
sex hormones
title Sex chromosome gene expression associated with vocal learning following hormonal manipulation in female zebra finches
title_full Sex chromosome gene expression associated with vocal learning following hormonal manipulation in female zebra finches
title_fullStr Sex chromosome gene expression associated with vocal learning following hormonal manipulation in female zebra finches
title_full_unstemmed Sex chromosome gene expression associated with vocal learning following hormonal manipulation in female zebra finches
title_short Sex chromosome gene expression associated with vocal learning following hormonal manipulation in female zebra finches
title_sort sex chromosome gene expression associated with vocal learning following hormonal manipulation in female zebra finches
topic T. castanotis
vocal learning
T. guttata
sex difference
sex chromosomes
sex hormones
url https://elifesciences.org/articles/89425
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AT hanachoe sexchromosomegeneexpressionassociatedwithvocallearningfollowinghormonalmanipulationinfemalezebrafinches
AT hiroakimatsunami sexchromosomegeneexpressionassociatedwithvocallearningfollowinghormonalmanipulationinfemalezebrafinches
AT erichjarvis sexchromosomegeneexpressionassociatedwithvocallearningfollowinghormonalmanipulationinfemalezebrafinches