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Cited by 149Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

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

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Ataman, Bulent, Boulting, Gabriella L., Harmin, David A., Yang, Marty G., Baker-Salisbury, Mollie, Yap, Ee-Lynn, Malik, Athar N., Mei, Kevin +16 more·2016·Nature
DOI 10.1038/nature20111PMC PMC5499253
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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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  • OSTN encodes osteocrin, a hormone that regulates dendritic growth in cerebral cortex, and has enhanced expression in the cerebral cortex.

    “OSTN encodes a hormone (osteocrin) that regulates dendritic growth in cerebral cortex (Ataman et al, 2016), with enhanced expression in the cerebral cortex (according to The Human Protein Atlas).”

    From The genetic regulation of protein expression in cerebrospinal fluid (2023) · cites this paper as Ataman et al, 2016

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Authors
Ataman, B., Boulting, G. L., Harmin, D. A., Yang, M. G., Baker-Salisbury, M., Yap, E.-L., Malik, A. N., Mei, K., Rubin, A. A., Spiegel, I., Durresi, E., Sharma, N., Hu, L. S., Pletikos, M., Griffith, E. C., Partlow, J. N., Stevens, C. R., Adli, M., Chahrour, M., Sestan, N., Walsh, C. A., Berezovskii, V. K., Livingstone, M. S., & Greenberg, M. E.
Affiliations
  • Harvard University (US)
  • Yale University (US)
  • Boston Children's Hospital (US)
  • Broad Institute (US)
  • University of Virginia (US)
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Greenberg, Michael E.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2016-11
Volume
539
Issue
7628
Pages
242-247
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature20111
PMC
PMC5499253
OpenAlex
W2556829211
Cited by
149
References
7
Citations by year
2026: 9 · 2025: 23 · 2024: 20 · 2023: 16 · 2022: 14 · 2021: 12 · 2020: 14 · 2019: 19 · 2018: 9 · 2017: 10 · 2016: 3
FWCI
9.17
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health (5rc2mh089952-02)
  • National Institute of Mental Health (RC2-MH089952, P50MH106933)
  • National Eye Institute (R01EY016187, P30EY012196)
  • National Institute of General Medical Sciences (T32GM007753)
  • National Institute of Neurological Disorders and Stroke (F32NS086270)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
osteocrin, primate brain evolution, neocortex, dendritic growth, MEF2 transcription factors, gene regulatory elements, secreted proteins, neuronal development, human fetal brain, macaque
MeSH terms
Animals, Base Sequence, Bone and Bones, Dendrites, Enhancer Elements, Genetic, Female, Humans, Macaca mulatta, Male, Molecular Sequence Data, Muscle Proteins, Muscles, Neurons, Organ Specificity, Species Specificity, Transcription Factors, Evolution, Molecular, Neocortex, Mice, Transcriptome, MEF2 Transcription Factors

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