A transgenic toolkit for visualizing and perturbing microtubules reveals unexpected functions in the epidermis
A transgenic toolkit for visualizing and perturbing microtubules reveals unexpected functions in the epidermis
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DOI：
10.7554/elife.29834
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发表时间：
2017-09-04
期刊：
影响因子：
7.7
通讯作者：
Lechler, Terry
中科院分区：
文献类型：
--
作者：
Muroyama, Andrew;Lechler, Terry
微管（MT）的生理功能在许多分化的细胞类型知之甚少。我们开发了一个遗传工具包来研究MT在不同细胞中的动力学和功能。使用TRE-EB 1-GFP小鼠，我们发现由于生长速率和寿命的改变，MT动力学在分化的角质形成细胞中以两个不同的步骤被强烈抑制。为了了解这些MT群体的功能，我们开发了TRE-spastin小鼠来破坏特定细胞类型中的MT。有丝分裂后角质形成细胞中的MT扰动对表皮形态发生有深远的影响。我们将细胞扁平化中的细胞自主作用与MT在调节增殖、分化和组织结构中的非细胞自主要求分开。这项工作揭示了MT在表皮发育中的生理作用，这里描述的工具将广泛用于研究MT在哺乳动物中的动态和功能。
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.