Emergence of sex-specific transcriptomes in a sexually-dimorphic brain nucleus

Sexual dimorphisms in the brain give rise to sex differences in physiology and behavior, yet we have limited understanding of the transcriptomic changes underlying their development. We evaluated developmental transcriptome dynamics for one of the most extreme neuroanatomical sexual dimorphisms in vertebrates - the songbird robust nucleus of the arcopallium (RA). RA is the telencephalic motor output nucleus of the song system. It grows monomorphically for the first few weeks posthatch, then continues growing in males but regresses in females, becoming 5-7 times larger in males. We quantified RA gene expression from monomorphic and dimorphic stages of development in both sexes. Mirroring the morphology, male and female transcriptomes initially resembled one other, then diverged markedly. Thousands of genes showed developmental regulation, corresponding to highly sex-specific biological processes. Males showed enrichments for neuronal growth and morphogenesis, synapse organization, metabolism, and voltage-gated ion channels. Females showed enrichments for cell polarity and differentiation, chemotaxis inhibition, gene silencing, and hormone and immune signaling. Notably, the majority of sex-biased genes in monomorphic RA were sex chromosome Z genes. These findings reveal a profound, sex-specific reorganization of RA's transcriptome, providing novel insights into potential targets and drivers of sexually dimorphic neurodevelopment. Overall design: mRNA profiles of brain nucleus RA from 20 DPH and 50 DPH male and female zebra finches