Convergent differential regulation of SLIT-ROBO axon guidance genes in the brains of vocal learners.
Abstract
Only a few distantly related mammals and birds have the trait of complex vocal learning,
which is the ability to imitate novel sounds. This ability is critical for speech
acquisition and production in humans, and is attributed to specialized forebrain vocal
control circuits that have several unique connections relative to adjacent brain circuits.
As a result, it has been hypothesized that there could exist convergent changes in
genes involved in neural connectivity of vocal learning circuits. In support of this
hypothesis, expanding on our related study (Pfenning et al. [2014] Science 346: 1256846),
here we show that the forebrain part of this circuit that makes a relatively rare
direct connection to brainstem vocal motor neurons in independent lineages of vocal
learning birds (songbird, parrot, and hummingbird) has specialized regulation of axon
guidance genes from the SLIT-ROBO molecular pathway. The SLIT1 ligand was differentially
downregulated in the motor song output nucleus that makes the direct projection, whereas
its receptor ROBO1 was developmentally upregulated during critical periods for vocal
learning. Vocal nonlearning bird species and male mice, which have much more limited
vocal plasticity and associated circuits, did not show comparable specialized regulation
of SLIT-ROBO genes in their nonvocal motor cortical regions. These findings are consistent
with SLIT and ROBO gene dysfunctions associated with autism, dyslexia, and speech
sound language disorders and suggest that convergent evolution of vocal learning was
associated with convergent changes in the SLIT-ROBO axon guidance pathway.
Type
Journal articleSubject
axon guidancehummingbird
neural connectivity
parrot
songbird
vocal learning
Age Factors
Animals
Axons
Birds
Brain
Female
Gene Expression Regulation
Glycoproteins
Learning
Male
Mice
Mice, Inbred C57BL
Nerve Tissue Proteins
Neurons
RNA, Messenger
Receptors, Immunologic
Vocalization, Animal
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https://hdl.handle.net/10161/11125Published Version (Please cite this version)
10.1002/cne.23719Publication Info
Wang, Rui; Chen, Chun-Chun; Hara, Erina; Rivas, Miriam V; Roulhac, Petra L; Howard,
Jason T; ... Jarvis, Erich D (2015). Convergent differential regulation of SLIT-ROBO axon guidance genes in the brains
of vocal learners. J Comp Neurol, 523(6). pp. 892-906. 10.1002/cne.23719. Retrieved from https://hdl.handle.net/10161/11125.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Erich David Jarvis
Adjunct Professor in the Deptartment of Neurobiology
Dr. Jarvis' laboratory studies the neurobiology of vocal communication. Emphasis is
placed on the molecular pathways involved in the perception and production of learned
vocalizations. They use an integrative approach that combines behavioral, anatomical,
electrophysiological and molecular biological techniques. The main animal model used
is songbirds, one of the few vertebrate groups that evolved the ability to learn vocalizations.
The generality of the discoveries is tested in other vocal lear

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