PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia. / Monroe, Tanner O.; Garrett, Melanie E.; Kousi, Maria; Rodriguiz, Ramona M.; Moon, Sungjin; Bai, Yushi; Brodar, Steven C.; Soldano, Karen L.; Savage, Jeremiah; Hansen, Thomas F.; Muzny, Donna M.; Gibbs, Richard A.; Barak, Lawrence; Sullivan, Patrick F.; Ashley-Koch, Allison E.; Sawa, Akira; Wetsel, William C.; Werge, Thomas; Katsanis, Nicholas.

In: Nature Communications, Vol. 11, No. 1, 5903, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Monroe, TO, Garrett, ME, Kousi, M, Rodriguiz, RM, Moon, S, Bai, Y, Brodar, SC, Soldano, KL, Savage, J, Hansen, TF, Muzny, DM, Gibbs, RA, Barak, L, Sullivan, PF, Ashley-Koch, AE, Sawa, A, Wetsel, WC, Werge, T & Katsanis, N 2020, 'PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia', Nature Communications, vol. 11, no. 1, 5903. https://doi.org/10.1038/s41467-020-19637-5

APA

Monroe, T. O., Garrett, M. E., Kousi, M., Rodriguiz, R. M., Moon, S., Bai, Y., Brodar, S. C., Soldano, K. L., Savage, J., Hansen, T. F., Muzny, D. M., Gibbs, R. A., Barak, L., Sullivan, P. F., Ashley-Koch, A. E., Sawa, A., Wetsel, W. C., Werge, T., & Katsanis, N. (2020). PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia. Nature Communications, 11(1), [5903]. https://doi.org/10.1038/s41467-020-19637-5

Vancouver

Monroe TO, Garrett ME, Kousi M, Rodriguiz RM, Moon S, Bai Y et al. PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia. Nature Communications. 2020;11(1). 5903. https://doi.org/10.1038/s41467-020-19637-5

Author

Monroe, Tanner O. ; Garrett, Melanie E. ; Kousi, Maria ; Rodriguiz, Ramona M. ; Moon, Sungjin ; Bai, Yushi ; Brodar, Steven C. ; Soldano, Karen L. ; Savage, Jeremiah ; Hansen, Thomas F. ; Muzny, Donna M. ; Gibbs, Richard A. ; Barak, Lawrence ; Sullivan, Patrick F. ; Ashley-Koch, Allison E. ; Sawa, Akira ; Wetsel, William C. ; Werge, Thomas ; Katsanis, Nicholas. / PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia. In: Nature Communications. 2020 ; Vol. 11, No. 1.

Bibtex

@article{275b7530f25e4d78a15feb8be557d886,
title = "PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia",
abstract = "The neuronal primary cilium and centriolar satellites have functions in neurogenesis, but little is known about their roles in the postnatal brain. We show that ablation of pericentriolar material 1 in the mouse leads to progressive ciliary, anatomical, psychomotor, and cognitive abnormalities. RNAseq reveals changes in amine- and G-protein coupled receptor pathways. The physiological relevance of this phenotype is supported by decreased available dopamine D2 receptor (D2R) levels and the failure of antipsychotic drugs to rescue adult behavioral defects. Immunoprecipitations show an association with Pcm1 and D2Rs. Finally, we sequence PCM1 in two human cohorts with severe schizophrenia. Systematic modeling of all discovered rare alleles by zebrafish in vivo complementation reveals an enrichment for pathogenic alleles. Our data emphasize a role for the pericentriolar material in the postnatal brain, with progressive degenerative ciliary and behavioral phenotypes; and they support a contributory role for PCM1 in some individuals diagnosed with schizophrenia. The role of ciliary/centriolar components in the postnatal brain is unclear. Here, the authors show via ablation of Pcm1 in mice that degenerative ciliary/centriolar phenotypes induce neuroanatomical and behavioral changes. Sequencing of PCM1 in human cohorts and zebrafish in vivo complementation suggests PCM1 mutations can contribute to schizophrenia.",
keywords = "GENETIC ASSOCIATION, HYDROCEPHALUS, METAANALYSIS, CENTROSOME, MUTATIONS, DISEASE, RARE, REPLICATION, RECRUITMENT, FRAMEWORK",
author = "Monroe, {Tanner O.} and Garrett, {Melanie E.} and Maria Kousi and Rodriguiz, {Ramona M.} and Sungjin Moon and Yushi Bai and Brodar, {Steven C.} and Soldano, {Karen L.} and Jeremiah Savage and Hansen, {Thomas F.} and Muzny, {Donna M.} and Gibbs, {Richard A.} and Lawrence Barak and Sullivan, {Patrick F.} and Ashley-Koch, {Allison E.} and Akira Sawa and Wetsel, {William C.} and Thomas Werge and Nicholas Katsanis",
year = "2020",
doi = "10.1038/s41467-020-19637-5",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia

AU - Monroe, Tanner O.

AU - Garrett, Melanie E.

AU - Kousi, Maria

AU - Rodriguiz, Ramona M.

AU - Moon, Sungjin

AU - Bai, Yushi

AU - Brodar, Steven C.

AU - Soldano, Karen L.

AU - Savage, Jeremiah

AU - Hansen, Thomas F.

AU - Muzny, Donna M.

AU - Gibbs, Richard A.

AU - Barak, Lawrence

AU - Sullivan, Patrick F.

AU - Ashley-Koch, Allison E.

AU - Sawa, Akira

AU - Wetsel, William C.

AU - Werge, Thomas

AU - Katsanis, Nicholas

PY - 2020

Y1 - 2020

N2 - The neuronal primary cilium and centriolar satellites have functions in neurogenesis, but little is known about their roles in the postnatal brain. We show that ablation of pericentriolar material 1 in the mouse leads to progressive ciliary, anatomical, psychomotor, and cognitive abnormalities. RNAseq reveals changes in amine- and G-protein coupled receptor pathways. The physiological relevance of this phenotype is supported by decreased available dopamine D2 receptor (D2R) levels and the failure of antipsychotic drugs to rescue adult behavioral defects. Immunoprecipitations show an association with Pcm1 and D2Rs. Finally, we sequence PCM1 in two human cohorts with severe schizophrenia. Systematic modeling of all discovered rare alleles by zebrafish in vivo complementation reveals an enrichment for pathogenic alleles. Our data emphasize a role for the pericentriolar material in the postnatal brain, with progressive degenerative ciliary and behavioral phenotypes; and they support a contributory role for PCM1 in some individuals diagnosed with schizophrenia. The role of ciliary/centriolar components in the postnatal brain is unclear. Here, the authors show via ablation of Pcm1 in mice that degenerative ciliary/centriolar phenotypes induce neuroanatomical and behavioral changes. Sequencing of PCM1 in human cohorts and zebrafish in vivo complementation suggests PCM1 mutations can contribute to schizophrenia.

AB - The neuronal primary cilium and centriolar satellites have functions in neurogenesis, but little is known about their roles in the postnatal brain. We show that ablation of pericentriolar material 1 in the mouse leads to progressive ciliary, anatomical, psychomotor, and cognitive abnormalities. RNAseq reveals changes in amine- and G-protein coupled receptor pathways. The physiological relevance of this phenotype is supported by decreased available dopamine D2 receptor (D2R) levels and the failure of antipsychotic drugs to rescue adult behavioral defects. Immunoprecipitations show an association with Pcm1 and D2Rs. Finally, we sequence PCM1 in two human cohorts with severe schizophrenia. Systematic modeling of all discovered rare alleles by zebrafish in vivo complementation reveals an enrichment for pathogenic alleles. Our data emphasize a role for the pericentriolar material in the postnatal brain, with progressive degenerative ciliary and behavioral phenotypes; and they support a contributory role for PCM1 in some individuals diagnosed with schizophrenia. The role of ciliary/centriolar components in the postnatal brain is unclear. Here, the authors show via ablation of Pcm1 in mice that degenerative ciliary/centriolar phenotypes induce neuroanatomical and behavioral changes. Sequencing of PCM1 in human cohorts and zebrafish in vivo complementation suggests PCM1 mutations can contribute to schizophrenia.

KW - GENETIC ASSOCIATION

KW - HYDROCEPHALUS

KW - METAANALYSIS

KW - CENTROSOME

KW - MUTATIONS

KW - DISEASE

KW - RARE

KW - REPLICATION

KW - RECRUITMENT

KW - FRAMEWORK

U2 - 10.1038/s41467-020-19637-5

DO - 10.1038/s41467-020-19637-5

M3 - Journal article

C2 - 33214552

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 5903

ER -

ID: 254994947