Urotensin-related gene transcripts mark developmental emergence of the male forebrain vocal control system in songbirds

Zachary W Bell,Peter Lovell,Ping K Yip,Claudio V Mello,David F Clayton,Julia M George

doi:10.1038/s41598-018-37057-w

Zachary W Bell, Peter Lovell + Show 4 more

Open Access

https://doi.org/10.1038/s41598-018-37057-w

Copy DOI

Abstract

Songbirds communicate through learned vocalizations, using a forebrain circuit with convergent similarity to vocal-control circuitry in humans. This circuit is incomplete in female zebra finches, hence only males sing. We show that the UTS2B gene, encoding Urotensin-Related Peptide (URP), is uniquely expressed in a key pre-motor vocal nucleus (HVC), and specifically marks the neurons that form a male-specific projection that encodes timing features of learned song. UTS2B-expressing cells appear early in males, prior to projection formation, but are not observed in the female nucleus. We find no expression evidence for canonical receptors within the vocal circuit, suggesting either signalling to other brain regions via diffusion or transduction through other receptor systems. Urotensins have not previously been implicated in vocal control, but we find an annotation in Allen Human Brain Atlas of increased UTS2B expression within portions of human inferior frontal cortex implicated in human speech and singing. Thus UTS2B (URP) is a novel neural marker that may have conserved functions for vocal communication.

Highlights

Vocal learning ability is a distinctive trait shared by humans and songbirds and only a few other animal groups[1]
What might be the potential significance of UTS2B expression in the songbird vocal control circuit? Is it expressed in a discrete cell population within HVC? Are urotensinergic receptors present in HVC or its targets? Is UTS2B expression correlated with adult function of the circuit, or might it have some role in circuit development? To address these questions, we annotated the urotensinergic gene family in the zebra finch and used in situ hybridization (ISH) and immunohistochemistry to map UTS2B expression at the cellular level throughout the zebra finch brain, along with neuronal tract-tracing to determine the identity of UTS2B-expressing cells in HVC
We found that the two peptide precursor genes, UTS2 (Entrez Gene 100222633) and UTS2B (Entrez Gene 100218300), were already correctly annotated in Taeniopygia_guttata-3.2.4; we confirmed their presence as single genes with two alleles each in Tgut_diploid_1.0 (Supplementary Annotation File)

Summary

Introduction

Vocal learning ability is a distinctive trait shared by humans and songbirds and only a few other animal groups[1]. Songbirds provide an important animal model for defining common molecular and physiological features of brain systems needed for vocal learning. In both humans and songbirds, vocal learning is controlled by specialized circuits that share similar connections and molecular properties[2,3]. We evaluated expression of the other main elements of the urotensinergic system (UTS2 and the canonical urotensin receptors) and analyzed expression of UTS2B during the developmental period when HVC undergoes marked changes in connectivity and function in concert with changes in vocal/singing behavior. Using data from the Allen Human Brain Atlas[32], we assessed whether UTS2B expression might occur in regions of the human brain involved in vocal control

Methods

Results

Conclusion