Evolution of Osteocrin as an activity-regulated factor in the primate brain.
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.
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Bulent
B
Ataman
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Gabriella L
GL
Boulting
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
David A
DA
Harmin
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Marty G
MG
Yang
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mollie
M
Baker-Salisbury
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Ee-Lynn
EL
Yap
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Athar N
AN
Malik
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Kevin
K
Mei
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Alex A
AA
Rubin
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Ivo
I
Spiegel
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Ershela
E
Durresi
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nikhil
N
Sharma
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Linda S
LS
Hu
Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510, USA.
Mihovil
M
Pletikos
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Eric C
EC
Griffith
Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Jennifer N
JN
Partlow
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Christine R
CR
Stevens
University of Virginia, School of Medicine, Department of Biochemistry and Molecular Genetics, Charlottesville, Virginia 22903, USA.
Mazhar
M
Adli
McDermott Center for Human Growth and Development, Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Maria
M
Chahrour
Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510, USA.
Nenad
N
Sestan
Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Christopher A
CA
Walsh
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Vladimir K
VK
Berezovskii
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Margaret S
MS
Livingstone
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Michael E
ME
Greenberg
D000818:Animals; D001483:Base Sequence; D001842:Bone and Bones / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D064326:MEF2 Transcription Factors / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D019579:Neocortex / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009928:Organ Specificity; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
D064326:MEF2 Transcription Factors; D009124:Muscle Proteins; C480236:OSTN protein, human; C498449:Ostn protein, mouse; D014157:Transcription Factors