Mitotic spindle regulation by Nde1 controls cerebral cortical size

Yuanyi Feng; Christopher A. Walsh

doi:10.1016/j.neuron.2004.09.023

Mitotic spindle regulation by Nde1 controls cerebral cortical size

Yuanyi Feng, Christopher A. Walsh^*

^*Corresponding author for this work

Neurology

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

302 Scopus citations

Abstract

Ablation of the LIS1-interacting protein Nde1 (formerly mNudE) in mouse produces a small brain (microcephaly), with the most dramatic reduction affecting the cerebral cortex. While cortical lamination is mostly preserved, the mutant cortex has fewer neurons and very thin superficial cortical layers (II to IV). BrdU birthdating revealed retarded and modestly disorganized neuronal migration; however, more dramatic defects on mitotic progression, mitotic orientation, and mitotic chromosome localization in cortical progenitors were observed in Nde1 mutant embryos. The small cerebral cortex seems to reflect both reduced progenitor cell division and altered neuronal cell fates. In vitro analysis demonstrated that Nde1 is essential for centrosome duplication and mitotic spindle assembly. Our data show that mitotic spindle function and orientation are essential for normal development of mammalian cerebral cortex.

Original language	English (US)
Pages (from-to)	279-293
Number of pages	15
Journal	Neuron
Volume	44
Issue number	2
DOIs	https://doi.org/10.1016/j.neuron.2004.09.023
State	Published - Oct 14 2004

Funding

We would like to thank members of the Walsh lab for stimulating discussions. Special gratitude goes to J. Corbo for constructing the backbone of the gene-targeting vector used in this study as well as his help in screening the mouse genomic library; Tam Thompson at the Center for Mental Retardation at the Children's Hospital of Boston (supported by NICDH P30HD18655) for assistance in generating Nde1-targeted mouse ES cells; and Dr. Arlene Sharp and Lina Du (Brigham and Women's Hospital) for mouse blastocyst injections. We are also grateful to Dr. Marc Kirschner (Harvard Medical School) for reading and providing helpful comments on an earlier version of the manuscript; to Drs. Paul Chang (Tim Mitchison lab, Harvard Medical School) and Robert Hevner (University of Washington) for sharing centrin and Tbr1 antibodies. This work was supported by research grants from the NINDS to C.A.W. (P01 NS40043 and RO1 NS032457). C.A.W. is an investigator of the Howard Hughes Medical Institute. Y.F. is supported by an award from NIMH (K01MH065338) and a postdoctoral fellowship from the Charles A. King Trust.

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1016/j.neuron.2004.09.023

Cite this

@article{6ebe7a062b0e408ba1a8a817849e8009,

title = "Mitotic spindle regulation by Nde1 controls cerebral cortical size",

abstract = "Ablation of the LIS1-interacting protein Nde1 (formerly mNudE) in mouse produces a small brain (microcephaly), with the most dramatic reduction affecting the cerebral cortex. While cortical lamination is mostly preserved, the mutant cortex has fewer neurons and very thin superficial cortical layers (II to IV). BrdU birthdating revealed retarded and modestly disorganized neuronal migration; however, more dramatic defects on mitotic progression, mitotic orientation, and mitotic chromosome localization in cortical progenitors were observed in Nde1 mutant embryos. The small cerebral cortex seems to reflect both reduced progenitor cell division and altered neuronal cell fates. In vitro analysis demonstrated that Nde1 is essential for centrosome duplication and mitotic spindle assembly. Our data show that mitotic spindle function and orientation are essential for normal development of mammalian cerebral cortex.",

author = "Yuanyi Feng and Walsh, {Christopher A.}",

note = "Funding Information: We would like to thank members of the Walsh lab for stimulating discussions. Special gratitude goes to J. Corbo for constructing the backbone of the gene-targeting vector used in this study as well as his help in screening the mouse genomic library; Tam Thompson at the Center for Mental Retardation at the Children's Hospital of Boston (supported by NICDH P30HD18655) for assistance in generating Nde1-targeted mouse ES cells; and Dr. Arlene Sharp and Lina Du (Brigham and Women's Hospital) for mouse blastocyst injections. We are also grateful to Dr. Marc Kirschner (Harvard Medical School) for reading and providing helpful comments on an earlier version of the manuscript; to Drs. Paul Chang (Tim Mitchison lab, Harvard Medical School) and Robert Hevner (University of Washington) for sharing centrin and Tbr1 antibodies. This work was supported by research grants from the NINDS to C.A.W. (P01 NS40043 and RO1 NS032457). C.A.W. is an investigator of the Howard Hughes Medical Institute. Y.F. is supported by an award from NIMH (K01MH065338) and a postdoctoral fellowship from the Charles A. King Trust. ",

year = "2004",

month = oct,

day = "14",

doi = "10.1016/j.neuron.2004.09.023",

language = "English (US)",

volume = "44",

pages = "279--293",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - Mitotic spindle regulation by Nde1 controls cerebral cortical size

AU - Feng, Yuanyi

AU - Walsh, Christopher A.

N1 - Funding Information: We would like to thank members of the Walsh lab for stimulating discussions. Special gratitude goes to J. Corbo for constructing the backbone of the gene-targeting vector used in this study as well as his help in screening the mouse genomic library; Tam Thompson at the Center for Mental Retardation at the Children's Hospital of Boston (supported by NICDH P30HD18655) for assistance in generating Nde1-targeted mouse ES cells; and Dr. Arlene Sharp and Lina Du (Brigham and Women's Hospital) for mouse blastocyst injections. We are also grateful to Dr. Marc Kirschner (Harvard Medical School) for reading and providing helpful comments on an earlier version of the manuscript; to Drs. Paul Chang (Tim Mitchison lab, Harvard Medical School) and Robert Hevner (University of Washington) for sharing centrin and Tbr1 antibodies. This work was supported by research grants from the NINDS to C.A.W. (P01 NS40043 and RO1 NS032457). C.A.W. is an investigator of the Howard Hughes Medical Institute. Y.F. is supported by an award from NIMH (K01MH065338) and a postdoctoral fellowship from the Charles A. King Trust.

PY - 2004/10/14

Y1 - 2004/10/14

N2 - Ablation of the LIS1-interacting protein Nde1 (formerly mNudE) in mouse produces a small brain (microcephaly), with the most dramatic reduction affecting the cerebral cortex. While cortical lamination is mostly preserved, the mutant cortex has fewer neurons and very thin superficial cortical layers (II to IV). BrdU birthdating revealed retarded and modestly disorganized neuronal migration; however, more dramatic defects on mitotic progression, mitotic orientation, and mitotic chromosome localization in cortical progenitors were observed in Nde1 mutant embryos. The small cerebral cortex seems to reflect both reduced progenitor cell division and altered neuronal cell fates. In vitro analysis demonstrated that Nde1 is essential for centrosome duplication and mitotic spindle assembly. Our data show that mitotic spindle function and orientation are essential for normal development of mammalian cerebral cortex.

AB - Ablation of the LIS1-interacting protein Nde1 (formerly mNudE) in mouse produces a small brain (microcephaly), with the most dramatic reduction affecting the cerebral cortex. While cortical lamination is mostly preserved, the mutant cortex has fewer neurons and very thin superficial cortical layers (II to IV). BrdU birthdating revealed retarded and modestly disorganized neuronal migration; however, more dramatic defects on mitotic progression, mitotic orientation, and mitotic chromosome localization in cortical progenitors were observed in Nde1 mutant embryos. The small cerebral cortex seems to reflect both reduced progenitor cell division and altered neuronal cell fates. In vitro analysis demonstrated that Nde1 is essential for centrosome duplication and mitotic spindle assembly. Our data show that mitotic spindle function and orientation are essential for normal development of mammalian cerebral cortex.

UR - http://www.scopus.com/inward/record.url?scp=5144222593&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=5144222593&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2004.09.023

DO - 10.1016/j.neuron.2004.09.023

M3 - Article

C2 - 15473967

AN - SCOPUS:5144222593

SN - 0896-6273

VL - 44

SP - 279

EP - 293

JO - Neuron

JF - Neuron

IS - 2

ER -

Mitotic spindle regulation by Nde1 controls cerebral cortical size

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this