A transgenic toolkit for visualizing and perturbing microtubules reveals unexpected functions in the epidermis

The physiological functions of microtubules (MTs) are poorly understood in many differentiated cell types. We developed a genetic toolkit to study MT dynamics and function in diverse cells. Using TRE-EB1-GFP mice, we found that MT dynamics are strongly suppressed in differentiated keratinocytes in t...

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Main Authors: Andrew Muroyama, Terry Lechler
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2017-09-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/29834
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author Andrew Muroyama
Terry Lechler
author_facet Andrew Muroyama
Terry Lechler
author_sort Andrew Muroyama
collection DOAJ
description The physiological functions of microtubules (MTs) are poorly understood in many differentiated cell types. We developed a genetic toolkit to study MT dynamics and function in diverse cells. Using TRE-EB1-GFP mice, we found that MT dynamics are strongly suppressed in differentiated keratinocytes in two distinct steps due to alterations in both growth rate and lifetime. To understand the functions of these MT populations, we developed TRE-spastin mice to disrupt MTs in specific cell types. MT perturbation in post-mitotic keratinocytes had profound consequences on epidermal morphogenesis. We uncoupled cell-autonomous roles in cell flattening from non-cell-autonomous requirements for MTs in regulating proliferation, differentiation, and tissue architecture. This work uncovers physiological roles for MTs in epidermal development, and the tools described here will be broadly useful to study MT dynamics and functions in mammals.
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spelling doaj.art-3be6643c033b4561ad97d19ca5b670a02022-12-22T03:24:33ZengeLife Sciences Publications LtdeLife2050-084X2017-09-01610.7554/eLife.29834A transgenic toolkit for visualizing and perturbing microtubules reveals unexpected functions in the epidermisAndrew Muroyama0https://orcid.org/0000-0003-0701-212XTerry Lechler1https://orcid.org/0000-0003-3901-7013Department of Dermatology, Duke University Medical Center, Durham, United States; Department of Cell Biology, Duke University Medical Center, Durham, United StatesDepartment of Dermatology, Duke University Medical Center, Durham, United States; Department of Cell Biology, Duke University Medical Center, Durham, United StatesThe physiological functions of microtubules (MTs) are poorly understood in many differentiated cell types. We developed a genetic toolkit to study MT dynamics and function in diverse cells. Using TRE-EB1-GFP mice, we found that MT dynamics are strongly suppressed in differentiated keratinocytes in two distinct steps due to alterations in both growth rate and lifetime. To understand the functions of these MT populations, we developed TRE-spastin mice to disrupt MTs in specific cell types. MT perturbation in post-mitotic keratinocytes had profound consequences on epidermal morphogenesis. We uncoupled cell-autonomous roles in cell flattening from non-cell-autonomous requirements for MTs in regulating proliferation, differentiation, and tissue architecture. This work uncovers physiological roles for MTs in epidermal development, and the tools described here will be broadly useful to study MT dynamics and functions in mammals.https://elifesciences.org/articles/29834spastinmicrotubuleepidermisskinnon-centrosomaldifferentiation
spellingShingle Andrew Muroyama
Terry Lechler
A transgenic toolkit for visualizing and perturbing microtubules reveals unexpected functions in the epidermis
eLife
spastin
microtubule
epidermis
skin
non-centrosomal
differentiation
title A transgenic toolkit for visualizing and perturbing microtubules reveals unexpected functions in the epidermis
title_full A transgenic toolkit for visualizing and perturbing microtubules reveals unexpected functions in the epidermis
title_fullStr A transgenic toolkit for visualizing and perturbing microtubules reveals unexpected functions in the epidermis
title_full_unstemmed A transgenic toolkit for visualizing and perturbing microtubules reveals unexpected functions in the epidermis
title_short A transgenic toolkit for visualizing and perturbing microtubules reveals unexpected functions in the epidermis
title_sort transgenic toolkit for visualizing and perturbing microtubules reveals unexpected functions in the epidermis
topic spastin
microtubule
epidermis
skin
non-centrosomal
differentiation
url https://elifesciences.org/articles/29834
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AT terrylechler atransgenictoolkitforvisualizingandperturbingmicrotubulesrevealsunexpectedfunctionsintheepidermis
AT andrewmuroyama transgenictoolkitforvisualizingandperturbingmicrotubulesrevealsunexpectedfunctionsintheepidermis
AT terrylechler transgenictoolkitforvisualizingandperturbingmicrotubulesrevealsunexpectedfunctionsintheepidermis