Davenport Matthew, Choe Ha Na, Matsunami Hiroaki, Jarvis Erich
Laboratory Language Neurogenetics, The Rockefeller University, New York City, United States.
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States.
Elife. 2025 Jun 30;12:RP89425. doi: 10.7554/eLife.89425.
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.
斑胸草雀是具有性别二态性的声乐学习者。雄性通过模仿成熟的同种个体来学习唱歌，而雌性则不会。雌性缺乏歌声与发育过程中几个声乐学习脑区的部分萎缩和明显抑制有关。然而，当给予早期药理学雌激素治疗时，萎缩可以预防，并且雌性可以保留声乐学习能力。为了筛选这种性别二态性的候选驱动因素，我们对来自两性的歌声学习核相对于周围区域的特化进行了无偏转录组分析，用载体或雌激素处理直至30日龄，此时两性之间的差异在解剖学上变得明显。通过RNA测序对转录组进行分析，确定了与性别和雌激素操纵相关的歌声核特化基因表达模块。雌性的HVC和X区基因模块通过补充雌激素而特化，表现出在雄性中观察到的转录组特化的一个子集。雌性弓状皮质粗壮核（RA）和前巢皮质外侧大细胞核（LMAN）特化模块对雌激素的依赖性较小。雌性中雌激素诱导的基因模块在解剖发育功能方面富集，并且与几个Z性染色体基因的表达强烈相关。我们提出了一个假设，即这些Z染色体基因的剂量和表达降低会抑制歌声系统的完全发育，从而抑制歌声学习行为，而雌激素治疗可以部分挽救这种行为。
