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由Mef2c-F10N增强子驱动的β-半乳糖苷酶(LacZ)和Cre重组酶小鼠有助于分析神经嵴细胞中的基因功能和谱系命运。

Mef2c-F10N enhancer driven β-galactosidase (LacZ) and Cre recombinase mice facilitate analyses of gene function and lineage fate in neural crest cells.

作者信息

Aoto Kazushi, Sandell Lisa L, Butler Tjaden Naomi E, Yuen Kobe C, Watt Kristin E Noack, Black Brian L, Durnin Michael, Trainor Paul A

机构信息

Stowers Institute for Medical Research, Kansas City, MO 64110, USA.

University of Louisville, Department of Molecular, Cellular and Craniofacial Biology, School of Dentistry, Louisville, KY 40201, USA.

出版信息

Dev Biol. 2015 Jun 1;402(1):3-16. doi: 10.1016/j.ydbio.2015.02.022. Epub 2015 Mar 17.

Abstract

Neural crest cells (NCC) comprise a multipotent, migratory stem cell and progenitor population that gives rise to numerous cell and tissue types within a developing embryo, including craniofacial bone and cartilage, neurons and glia of the peripheral nervous system, and melanocytes within the skin. Here we describe two novel stable transgenic mouse lines suitable for lineage tracing and analysis of gene function in NCC. Firstly, using the F10N enhancer of the Mef2c gene (Mef2c-F10N) linked to LacZ, we generated transgenic mice (Mef2c-F10N-LacZ) that express LacZ in the majority, if not all migrating NCC that delaminate from the neural tube. Mef2c-F10N-LacZ then continues to be expressed primarily in neurogenic, gliogenic and melanocytic NCC and their derivatives, but not in ectomesenchymal derivatives. Secondly, we used the same Mef2c-F10N enhancer together with Cre recombinase to generate transgenic mice (Mef2c-F10N-Cre) that can be used to indelibly label, or alter gene function in, migrating NCC and their derivatives. At early stages of development, Mef2c-F10N-LacZ and Mef2c-F10N-Cre label NCC in a pattern similar to Wnt1-Cre mice, with the exception that Mef2c-F10N-LacZ and Mef2c-F10N-Cre specifically label NCC that have delaminated from the neural plate, while premigratory NCC are not labeled. Thus, our Mef2c-F10N-LacZ and Mef2c-F10N-Cre transgenic mice provide new resources for tracing migratory NCC and analyzing gene function in migrating and differentiating NCC independently of NCC formation.

摘要

神经嵴细胞(NCC)是一种多能性的迁移干细胞和祖细胞群体,在发育中的胚胎内可分化为众多细胞和组织类型,包括颅面骨和软骨、外周神经系统的神经元和神经胶质细胞,以及皮肤中的黑素细胞。在此,我们描述了两种适用于谱系追踪和分析NCC中基因功能的新型稳定转基因小鼠品系。首先,利用与LacZ相连的Mef2c基因的F10N增强子(Mef2c-F10N),我们构建了转基因小鼠(Mef2c-F10N-LacZ),这些小鼠在从神经管分层出来的大部分(如果不是全部)迁移NCC中表达LacZ。Mef2c-F10N-LacZ随后主要继续在神经源性、胶质源性和黑素细胞性NCC及其衍生物中表达,但在外胚间充质衍生物中不表达。其次,我们使用相同的Mef2c-F10N增强子与Cre重组酶构建了转基因小鼠(Mef2c-F10N-Cre),可用于对迁移的NCC及其衍生物进行永久性标记或改变其基因功能。在发育早期,Mef2c-F10N-LacZ和Mef2c-F10N-Cre标记NCC的模式与Wnt1-Cre小鼠相似,不同之处在于Mef2c-F10N-LacZ和Mef2c-F10N-Cre特异性标记从神经板分层出来的NCC,而迁移前的NCC未被标记。因此,我们的Mef2c-F10N-LacZ和Mef2c-F10N-Cre转基因小鼠为追踪迁移的NCC以及独立于NCC形成过程分析迁移和分化中的NCC的基因功能提供了新的资源。

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