2. Academic Validation
  3. Evolution of Osteocrin as an activity-regulated factor in the primate brain

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

  • Nature. 2016 Nov 10;539(7628):242-247. doi: 10.1038/nature20111.
Bulent Ataman 1,  Gabriella L Boulting 1,  David A Harmin 1,  Marty G Yang 1,  Mollie Baker-Salisbury 1,  Ee-Lynn Yap 1,  Athar N Malik 1,  Kevin Mei 1,  Alex A Rubin 1,  Ivo Spiegel 1,  Ershela Durresi 1,  Nikhil Sharma 1,  Linda S Hu 1,  Mihovil Pletikos 2,  Eric C Griffith 1,  Jennifer N Partlow 3,  Christine R Stevens 4,  Mazhar Adli 5,  Maria Chahrour 6,  Nenad Sestan 2,  Christopher A Walsh 3,  Vladimir K Berezovskii 1,  Margaret S Livingstone 1,  Michael E Greenberg 1
Affiliations

Affiliations

  • 1 Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • 2 Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510, USA.
  • 3 Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • 4 Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
  • 5 University of Virginia, School of Medicine, Department of Biochemistry and Molecular Genetics, Charlottesville, Virginia 22903, USA.
  • 6 McDermott Center for Human Growth and Development, Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
PMID: 27830782 DOI: 10.1038/nature20111
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.

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