Evolution of Osteocrin as an activity-regulated factor in the primate brain

Bulent Ataman, Gabriella L. Boulting, David A. Harmin, Marty G. Yang, Mollie Baker-Salisbury, Ee-Lynn Yap, Athar N. Malik, Kevin Mei, Alex A. Rubin, Ivo Spiegel, Ershela Durresi, Nikhil Sharma, Linda S. Hu, Mihovil Pletikos, Eric C. Griffith, Jennifer N. Partlow, Christine R. Stevens, Mazhar Adli, Maria Chahrour, Nenad Sestan, Christopher A. Walsh, Vladimir K. Berezovskii, Margaret S. Livingstone and Michael E. Greenberg ()
Additional contact information
Bulent Ataman: Harvard Medical School
Gabriella L. Boulting: Harvard Medical School
David A. Harmin: Harvard Medical School
Marty G. Yang: Harvard Medical School
Mollie Baker-Salisbury: Harvard Medical School
Ee-Lynn Yap: Harvard Medical School
Athar N. Malik: Harvard Medical School
Kevin Mei: Harvard Medical School
Alex A. Rubin: Harvard Medical School
Ivo Spiegel: Harvard Medical School
Ershela Durresi: Harvard Medical School
Nikhil Sharma: Harvard Medical School
Linda S. Hu: Harvard Medical School
Mihovil Pletikos: Yale School of Medicine
Eric C. Griffith: Harvard Medical School
Jennifer N. Partlow: Boston Children's Hospital, Harvard Medical School
Christine R. Stevens: Broad Institute of MIT and Harvard
Mazhar Adli: University of Virginia, School of Medicine
Maria Chahrour: McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center
Nenad Sestan: Yale School of Medicine
Christopher A. Walsh: Boston Children's Hospital, Harvard Medical School
Vladimir K. Berezovskii: Harvard Medical School
Margaret S. Livingstone: Harvard Medical School
Michael E. Greenberg: Harvard Medical School

Nature, 2016, vol. 539, issue 7628, 242-247

Abstract: Abstract Sensory stimuli drive the maturation and function of the mammalian nervous system in part through the activation of gene expression networks that regulate synapse development and plasticity. These networks have primarily been studied in mice, and it is not known whether there are species- or clade-specific activity-regulated genes that control features of brain development and function. Here we use transcriptional profiling of human fetal brain cultures to identify an activity-dependent secreted factor, Osteocrin (OSTN), that is induced by membrane depolarization of human but not mouse neurons. We find that OSTN has been repurposed in primates through the evolutionary acquisition of DNA regulatory elements that bind the activity-regulated transcription factor MEF2. In addition, we demonstrate that OSTN is expressed in primate neocortex and restricts activity-dependent dendritic growth in human neurons. These findings suggest that, in response to sensory input, OSTN regulates features of neuronal structure and function that are unique to primates.

Date: 2016
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DOI: 10.1038/nature20111

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