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; Michael E. Greenberg

doi:10.1038/nature20111

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 SestanChristopher A. Walsh, Vladimir K. Berezovskii, Margaret S. Livingstone, Michael E. Greenberg^*

^*Corresponding author for this work

Obstetrics and Gynecology

Research output: Contribution to journal › Article › peer-review

104 Scopus citations

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.

Original language	English (US)
Pages (from-to)	242-247
Number of pages	6
Journal	Nature
Volume	539
Issue number	7628
DOIs	https://doi.org/10.1038/nature20111
State	Published - Nov 9 2016

Funding

This work was supported by grants from the NIH: P50MH106933 and 1RC2MH089952 (M.E.G.), 5F32NS086270 (G.L.B.), EY16187 (M.S.L.), EY12196 (V.K.B.), and T32GM007753 (A.N.M. and E.D.). B.A. is supported by The Ellen R. and Melvin J. Gordon Center for the Cure and Treatment of Paralysis.

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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., ... Greenberg, M. E. (2016). Evolution of Osteocrin as an activity-regulated factor in the primate brain. Nature, 539(7628), 242-247. https://doi.org/10.1038/nature20111

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title = "Evolution of Osteocrin as an activity-regulated factor in the primate brain",

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.",

author = "Bulent Ataman and Boulting, {Gabriella L.} and Harmin, {David A.} and Yang, {Marty G.} and Mollie Baker-Salisbury and Yap, {Ee Lynn} and Malik, {Athar N.} and Kevin Mei and Rubin, {Alex A.} and Ivo Spiegel and Ershela Durresi and Nikhil Sharma and Hu, {Linda S.} and Mihovil Pletikos and Griffith, {Eric C.} and Partlow, {Jennifer N.} and Stevens, {Christine R.} and Mazhar Adli and Maria Chahrour and Nenad Sestan and Walsh, {Christopher A.} and Berezovskii, {Vladimir K.} and Livingstone, {Margaret S.} and Greenberg, {Michael E.}",

year = "2016",

month = nov,

day = "9",

doi = "10.1038/nature20111",

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Ataman, B, Boulting, GL, Harmin, DA, Yang, MG, Baker-Salisbury, M, Yap, EL, Malik, AN, Mei, K, Rubin, AA, Spiegel, I, Durresi, E, Sharma, N, Hu, LS, Pletikos, M, Griffith, EC, Partlow, JN, Stevens, CR, Adli, M, Chahrour, M, Sestan, N, Walsh, CA, Berezovskii, VK, Livingstone, MS & Greenberg, ME 2016, 'Evolution of Osteocrin as an activity-regulated factor in the primate brain', Nature, vol. 539, no. 7628, pp. 242-247. https://doi.org/10.1038/nature20111

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T1 - Evolution of Osteocrin as an activity-regulated factor in the primate brain

AU - Ataman, Bulent

AU - Boulting, Gabriella L.

AU - Harmin, David A.

AU - Yang, Marty G.

AU - Baker-Salisbury, Mollie

AU - Yap, Ee Lynn

AU - Malik, Athar N.

AU - Mei, Kevin

AU - Rubin, Alex A.

AU - Spiegel, Ivo

AU - Durresi, Ershela

AU - Sharma, Nikhil

AU - Hu, Linda S.

AU - Pletikos, Mihovil

AU - Griffith, Eric C.

AU - Partlow, Jennifer N.

AU - Stevens, Christine R.

AU - Adli, Mazhar

AU - Chahrour, Maria

AU - Sestan, Nenad

AU - Walsh, Christopher A.

AU - Berezovskii, Vladimir K.

AU - Livingstone, Margaret S.

AU - Greenberg, Michael E.

PY - 2016/11/9

Y1 - 2016/11/9

N2 - 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.

AB - 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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ER -

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

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