Convergent differential regulation of SLIT-ROBO axon guidance genes in the brains of vocal learners.
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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.  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.
Gene Expression Regulation
Mice, Inbred C57BL
Nerve Tissue Proteins
Published Version (Please cite this version)10.1002/cne.23719
Publication InfoWang, 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.
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Adjunct Professor in the Dept. 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