The kinetochore-microtubule coupling machinery is repurposed in sensory nervous system morphogenesis

Dhanya K Cheerambathur; Bram Prevo; Tiffany-Lynn Chow; Neil Hattersley; Shaohe Wang; Zhiling Zhao; Taekyung Kim; Adina Gerson-Gurwitz; Karen Oegema; Rebecca Green; Arshad Desai

doi:10.1016/j.devcel.2019.02.002

The kinetochore-microtubule coupling machinery is repurposed in sensory nervous system morphogenesis

Dhanya K Cheerambathur, Bram Prevo, Tiffany-Lynn Chow, Neil Hattersley, Shaohe Wang, Zhiling Zhao, Taekyung Kim, Adina Gerson-Gurwitz, Karen Oegema, Rebecca Green, Arshad Desai

School of Biological Sciences

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

Abstract / Description of output

Dynamic coupling of microtubule ends to kinetochores, built on the centromeres of chromosomes, directs chromosome segregation during cell division. Here, we report that the evolutionarily ancient kinetochore-microtubule coupling machine, the KMN (Knl1/Mis12/Ndc80-complex) network, plays a critical role in neuronal morphogenesis. We show that the KMN network concentrates in microtubule-rich dendrites of developing sensory neurons that collectively extend in a multicellular morphogenetic event that occurs during C. elegans embryogenesis. Post-mitotic degradation of KMN components in sensory neurons disrupts dendritic extension, leading to patterning and functional defects in the sensory nervous system. Structure-guided mutations revealed that the molecular interface that couples kinetochores to spindle microtubules also functions in neuronal development. These results identify a cell-division-independent function for the chromosome-segregation machinery and define a microtubule-coupling-dependent event in sensory nervous system morphogenesis.

Original language	English
Pages (from-to)	P864-872.E7
Number of pages	16
Journal	Developmental Cell
Volume	48
Issue number	6
Early online date	28 Feb 2019
DOIs	https://doi.org/10.1016/j.devcel.2019.02.002
Publication status	Published - 25 Mar 2019

Keywords / Materials (for Non-textual outputs)

KMN network
Knl1
Mis12 complex
Ndc80 complex
chromosome segregation
dendrite
kinetochore
microtubule
mitosis
morphogenesis
nervous system
sensory neuron

Access to Document

10.1016/j.devcel.2019.02.002Licence: Creative Commons: Attribution (CC-BY)

DesaiEtalDC2019TheKinetochoreMicrotubuleCouplingMachinery Final published version, 7.5 MBLicence: Creative Commons: Attribution (CC-BY)

`Core Funding for the Wellcome Trust Centre for Cell Biology¿, Research Enrichment, Public Engagement
Tollervey, D.
UK-based charities
1/12/18 → 1/06/22
Project: Research
Molecular mechanisms driving the formation of the neuronal microtubule cytoskeleton
Cheerambathur, D. & Tollervey, D.
UK-based charities
1/05/18 → 24/08/23
Project: Research

Dhanya Cheerambathur
- School of Biological Sciences - Sir Henry Dale Fellow
- Edinburgh Neuroscience
Person: Academic: Research Active

Cite this

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title = "The kinetochore-microtubule coupling machinery is repurposed in sensory nervous system morphogenesis",

abstract = "Dynamic coupling of microtubule ends to kinetochores, built on the centromeres of chromosomes, directs chromosome segregation during cell division. Here, we report that the evolutionarily ancient kinetochore-microtubule coupling machine, the KMN (Knl1/Mis12/Ndc80-complex) network, plays a critical role in neuronal morphogenesis. We show that the KMN network concentrates in microtubule-rich dendrites of developing sensory neurons that collectively extend in a multicellular morphogenetic event that occurs during C. elegans embryogenesis. Post-mitotic degradation of KMN components in sensory neurons disrupts dendritic extension, leading to patterning and functional defects in the sensory nervous system. Structure-guided mutations revealed that the molecular interface that couples kinetochores to spindle microtubules also functions in neuronal development. These results identify a cell-division-independent function for the chromosome-segregation machinery and define a microtubule-coupling-dependent event in sensory nervous system morphogenesis.",

keywords = "KMN network, Knl1, Mis12 complex, Ndc80 complex, chromosome segregation, dendrite, kinetochore, microtubule, mitosis, morphogenesis, nervous system, sensory neuron",

author = "Cheerambathur, {Dhanya K} and Bram Prevo and Tiffany-Lynn Chow and Neil Hattersley and Shaohe Wang and Zhiling Zhao and Taekyung Kim and Adina Gerson-Gurwitz and Karen Oegema and Rebecca Green and Arshad Desai",

year = "2019",

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doi = "10.1016/j.devcel.2019.02.002",

language = "English",

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AU - Cheerambathur, Dhanya K

AU - Prevo, Bram

AU - Chow, Tiffany-Lynn

AU - Hattersley, Neil

AU - Wang, Shaohe

AU - Zhao, Zhiling

AU - Kim, Taekyung

AU - Gerson-Gurwitz, Adina

AU - Oegema, Karen

AU - Green, Rebecca

AU - Desai, Arshad

PY - 2019/3/25

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N2 - Dynamic coupling of microtubule ends to kinetochores, built on the centromeres of chromosomes, directs chromosome segregation during cell division. Here, we report that the evolutionarily ancient kinetochore-microtubule coupling machine, the KMN (Knl1/Mis12/Ndc80-complex) network, plays a critical role in neuronal morphogenesis. We show that the KMN network concentrates in microtubule-rich dendrites of developing sensory neurons that collectively extend in a multicellular morphogenetic event that occurs during C. elegans embryogenesis. Post-mitotic degradation of KMN components in sensory neurons disrupts dendritic extension, leading to patterning and functional defects in the sensory nervous system. Structure-guided mutations revealed that the molecular interface that couples kinetochores to spindle microtubules also functions in neuronal development. These results identify a cell-division-independent function for the chromosome-segregation machinery and define a microtubule-coupling-dependent event in sensory nervous system morphogenesis.

AB - Dynamic coupling of microtubule ends to kinetochores, built on the centromeres of chromosomes, directs chromosome segregation during cell division. Here, we report that the evolutionarily ancient kinetochore-microtubule coupling machine, the KMN (Knl1/Mis12/Ndc80-complex) network, plays a critical role in neuronal morphogenesis. We show that the KMN network concentrates in microtubule-rich dendrites of developing sensory neurons that collectively extend in a multicellular morphogenetic event that occurs during C. elegans embryogenesis. Post-mitotic degradation of KMN components in sensory neurons disrupts dendritic extension, leading to patterning and functional defects in the sensory nervous system. Structure-guided mutations revealed that the molecular interface that couples kinetochores to spindle microtubules also functions in neuronal development. These results identify a cell-division-independent function for the chromosome-segregation machinery and define a microtubule-coupling-dependent event in sensory nervous system morphogenesis.

KW - KMN network

KW - Knl1

KW - Mis12 complex

KW - Ndc80 complex

KW - chromosome segregation

KW - dendrite

KW - kinetochore

KW - microtubule

KW - mitosis

KW - morphogenesis

KW - nervous system

KW - sensory neuron

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DO - 10.1016/j.devcel.2019.02.002

M3 - Article

C2 - 30827898

SN - 1534-5807

VL - 48

SP - P864-872.E7

JO - Developmental Cell

JF - Developmental Cell

IS - 6

ER -

The kinetochore-microtubule coupling machinery is repurposed in sensory nervous system morphogenesis

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

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Projects

`Core Funding for the Wellcome Trust Centre for Cell Biology¿, Research Enrichment, Public Engagement

Molecular mechanisms driving the formation of the neuronal microtubule cytoskeleton

Profiles

Dhanya Cheerambathur

Cite this