Rui Wang, Chun-Chun Chen, Erina Hara, Miriam V. Rivas, Petra L. Roulhac, Jason T. Howard, Mukta Chakraborty, Jean-Nicolas Audet, and and Erich D. Jarvis, 'Convergent Differential Regulation of SLIT-ROBO Axon Guidance Genes in the Brains of Vocal Learners', J Comparative Neurology (2014).
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 some 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, here we show that the forebrain to brainstem part of this circuit in independent lineages of vocal learning birds (songbird, parrot, and hummingbird) has specialized expression of axon guidance genes from the ROBO-SLIT molecular pathway. The ligand SLIT1 was down-regulated in the motor song output nucleus that makes the direct projection onto brainstem vocal motor neurons in vocal learners, whereas its receptor ROBO1 was developmentally regulated in the same forebrain nucleus during critical periods for vocal learning in zebra finch males but not in vocal non-learning females. Vocal non-learning bird species and male mice, which have much more limited vocal plasticity and associated circuits, did not show comparable specialized expression of ROBO-SLIT genes in their motor cortical regions. These findings are consistent with ROBO and SLIT gene dysfunctions associated with autism, dyslexia, and speech sound disorders and suggest that convergent evolution of vocal learning was associated with convergent changes in the ROBO–SLIT axon guidance pathway. We hypothesize that these genes could be related to the specialized connectivity of vocal learning circuits.