title: 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.
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina, 27710; Computational Biology and Bioinformatics Program, Institute for Genome Science and Policy, Duke University, Durham, North Carolina, 27710; Beijing Prosperous Biopharm, Beijing, 100085, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Chun-Chun
authors.initials: CC
authors.lastname: Chen
authors.forename: Erina
authors.initials: E
authors.lastname: Hara
authors.forename: Miriam V
authors.initials: MV
authors.lastname: Rivas
authors.forename: Petra L
authors.initials: PL
authors.lastname: Roulhac
authors.forename: Jason T
authors.initials: JT
authors.lastname: Howard
authors.forename: Mukta
authors.initials: M
authors.lastname: Chakraborty
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Audet
authors.forename: Erich D
authors.initials: ED
authors.lastname: Jarvis
mesh_terms: D000367:Age Factors; D000818:Animals; D001369:Axons / Q000502:physiology*; D001717:Birds / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D007858:Learning / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D014828:Vocalization, Animal / Q000502:physiology*; D000097905:Roundabout Proteins
chemical_list: D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C120566:slit protein, vertebrate
keywords: axon guidance; hummingbird; neural connectivity; parrot; songbird; vocal learning