RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis

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

Standard

RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis. / Farooq, Muhammad; Lindbæk, Louise; Krogh, Nicolai; Doganli, Canan; Keller, Cecilie; Mönnich, Maren; Gonçalves, André Brás; Sakthivel, Srinivasan; Mang, Yuan; Fatima, Ambrin; Andersen, Vivi Søgaard; Hussain, Muhammad S.; Eiberg, Hans; Hansen, Lars; Kjaer, Klaus Wilbrandt; Gopalakrishnan, Jay; Pedersen, Lotte Bang; Møllgård, Kjeld; Nielsen, Henrik; Baig, Shahid M.; Tommerup, Niels; Christensen, Søren Tvorup; Larsen, Lars Allan.

In: Nature Communications, Vol. 11, 5816, 2020.

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

Harvard

Farooq, M, Lindbæk, L, Krogh, N, Doganli, C, Keller, C, Mönnich, M, Gonçalves, AB, Sakthivel, S, Mang, Y, Fatima, A, Andersen, VS, Hussain, MS, Eiberg, H, Hansen, L, Kjaer, KW, Gopalakrishnan, J, Pedersen, LB, Møllgård, K, Nielsen, H, Baig, SM, Tommerup, N, Christensen, ST & Larsen, LA 2020, 'RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis', Nature Communications, vol. 11, 5816. https://doi.org/10.1038/s41467-020-19658-0

APA

Farooq, M., Lindbæk, L., Krogh, N., Doganli, C., Keller, C., Mönnich, M., Gonçalves, A. B., Sakthivel, S., Mang, Y., Fatima, A., Andersen, V. S., Hussain, M. S., Eiberg, H., Hansen, L., Kjaer, K. W., Gopalakrishnan, J., Pedersen, L. B., Møllgård, K., Nielsen, H., ... Larsen, L. A. (2020). RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis. Nature Communications, 11, [5816]. https://doi.org/10.1038/s41467-020-19658-0

Vancouver

Farooq M, Lindbæk L, Krogh N, Doganli C, Keller C, Mönnich M et al. RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis. Nature Communications. 2020;11. 5816. https://doi.org/10.1038/s41467-020-19658-0

Author

Farooq, Muhammad ; Lindbæk, Louise ; Krogh, Nicolai ; Doganli, Canan ; Keller, Cecilie ; Mönnich, Maren ; Gonçalves, André Brás ; Sakthivel, Srinivasan ; Mang, Yuan ; Fatima, Ambrin ; Andersen, Vivi Søgaard ; Hussain, Muhammad S. ; Eiberg, Hans ; Hansen, Lars ; Kjaer, Klaus Wilbrandt ; Gopalakrishnan, Jay ; Pedersen, Lotte Bang ; Møllgård, Kjeld ; Nielsen, Henrik ; Baig, Shahid M. ; Tommerup, Niels ; Christensen, Søren Tvorup ; Larsen, Lars Allan. / RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis. In: Nature Communications. 2020 ; Vol. 11.

Bibtex

@article{222a62fcfd86408da0d3deca8a8cceeb,
title = "RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis",
abstract = "Primary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability. The exact pathophysiological mechanism underlying MCPH remains to be elucidated, but dysfunction of neuronal progenitors in the developing neocortex plays a major role. We identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, segregating with MCPH in a consanguineous family with 10 affected individuals. RRP7A is highly expressed in neural stem cells in developing human forebrain, and targeted mutation of Rrp7a leads to defects in neurogenesis and proliferation in a mouse stem cell model. RRP7A localizes to centrosomes, cilia and nucleoli, and patient-derived fibroblasts display defects in ribosomal RNA processing, primary cilia resorption, and cell cycle progression. Analysis of zebrafish embryos supported that the patient mutation in RRP7A causes reduced brain size, impaired neurogenesis and cell proliferation, and defective ribosomal RNA processing. These findings provide novel insight into human brain development and MCPH.",
author = "Muhammad Farooq and Louise Lindb{\ae}k and Nicolai Krogh and Canan Doganli and Cecilie Keller and Maren M{\"o}nnich and Gon{\c c}alves, {Andr{\'e} Br{\'a}s} and Srinivasan Sakthivel and Yuan Mang and Ambrin Fatima and Andersen, {Vivi S{\o}gaard} and Hussain, {Muhammad S.} and Hans Eiberg and Lars Hansen and Kjaer, {Klaus Wilbrandt} and Jay Gopalakrishnan and Pedersen, {Lotte Bang} and Kjeld M{\o}llg{\aa}rd and Henrik Nielsen and Baig, {Shahid M.} and Niels Tommerup and Christensen, {S{\o}ren Tvorup} and Larsen, {Lars Allan}",
year = "2020",
doi = "10.1038/s41467-020-19658-0",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis

AU - Farooq, Muhammad

AU - Lindbæk, Louise

AU - Krogh, Nicolai

AU - Doganli, Canan

AU - Keller, Cecilie

AU - Mönnich, Maren

AU - Gonçalves, André Brás

AU - Sakthivel, Srinivasan

AU - Mang, Yuan

AU - Fatima, Ambrin

AU - Andersen, Vivi Søgaard

AU - Hussain, Muhammad S.

AU - Eiberg, Hans

AU - Hansen, Lars

AU - Kjaer, Klaus Wilbrandt

AU - Gopalakrishnan, Jay

AU - Pedersen, Lotte Bang

AU - Møllgård, Kjeld

AU - Nielsen, Henrik

AU - Baig, Shahid M.

AU - Tommerup, Niels

AU - Christensen, Søren Tvorup

AU - Larsen, Lars Allan

PY - 2020

Y1 - 2020

N2 - Primary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability. The exact pathophysiological mechanism underlying MCPH remains to be elucidated, but dysfunction of neuronal progenitors in the developing neocortex plays a major role. We identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, segregating with MCPH in a consanguineous family with 10 affected individuals. RRP7A is highly expressed in neural stem cells in developing human forebrain, and targeted mutation of Rrp7a leads to defects in neurogenesis and proliferation in a mouse stem cell model. RRP7A localizes to centrosomes, cilia and nucleoli, and patient-derived fibroblasts display defects in ribosomal RNA processing, primary cilia resorption, and cell cycle progression. Analysis of zebrafish embryos supported that the patient mutation in RRP7A causes reduced brain size, impaired neurogenesis and cell proliferation, and defective ribosomal RNA processing. These findings provide novel insight into human brain development and MCPH.

AB - Primary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability. The exact pathophysiological mechanism underlying MCPH remains to be elucidated, but dysfunction of neuronal progenitors in the developing neocortex plays a major role. We identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, segregating with MCPH in a consanguineous family with 10 affected individuals. RRP7A is highly expressed in neural stem cells in developing human forebrain, and targeted mutation of Rrp7a leads to defects in neurogenesis and proliferation in a mouse stem cell model. RRP7A localizes to centrosomes, cilia and nucleoli, and patient-derived fibroblasts display defects in ribosomal RNA processing, primary cilia resorption, and cell cycle progression. Analysis of zebrafish embryos supported that the patient mutation in RRP7A causes reduced brain size, impaired neurogenesis and cell proliferation, and defective ribosomal RNA processing. These findings provide novel insight into human brain development and MCPH.

U2 - 10.1038/s41467-020-19658-0

DO - 10.1038/s41467-020-19658-0

M3 - Journal article

C2 - 33199730

AN - SCOPUS:85096062397

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 5816

ER -

ID: 251939034