Kurland Meagan, O'Meara Bryn, Tucker Dana K, Ackley Brian D
Department of Molecular Biosciences, The University of Kansas, Lawrence, KS 66045, USA.
Department of Biology, The University of Central Missouri, Warrensburg, MO 64093, USA.
J Dev Biol. 2020 Mar 3;8(1):5. doi: 10.3390/jdb8010005.
Nervous systems are comprised of diverse cell types that differ functionally and morphologically. During development, extrinsic signals, e.g., growth factors, can activate intrinsic programs, usually orchestrated by networks of transcription factors. Within that network, transcription factors that drive the specification of features specific to a limited number of cells are often referred to as terminal selectors. While we still have an incomplete view of how individual neurons within organisms become specified, reporters limited to a subset of neurons in a nervous system can facilitate the discovery of cell specification programs. We have identified a fluorescent reporter that labels VD13, the most posterior of the 19 inhibitory GABA (γ-amino butyric acid)-ergic motorneurons, and two additional neurons, LUAL and LUAR. Loss of function in multiple Wnt signaling genes resulted in an incompletely penetrant loss of the marker, selectively in VD13, but not the LUAs, even though other aspects of GABAergic specification in VD13 were normal. The posterior Hox gene, , was necessary for expression of our marker in VD13, and ectopic expression of in more anterior GABAergic neurons induced expression of the marker. These results suggest is a terminal selector of VD13, subsequent to GABAergic specification.
神经系统由功能和形态各异的多种细胞类型组成。在发育过程中,外部信号,如生长因子,可激活通常由转录因子网络精心编排的内在程序。在该网络中,驱动特定数量细胞特有的特征形成的转录因子通常被称为终末选择因子。虽然我们对生物体中的单个神经元如何特化的认识仍不完整,但仅限于神经系统中一部分神经元的报告基因有助于发现细胞特化程序。我们鉴定出一种荧光报告基因,它标记VD13(19个抑制性γ-氨基丁酸能运动神经元中最靠后的一个)以及另外两个神经元LUAL和LUAR。多个Wnt信号基因功能丧失导致该标记物在VD13中选择性地不完全缺失,但在LUA神经元中没有缺失,尽管VD13中γ-氨基丁酸能特化的其他方面是正常的。后部Hox基因对于我们的标记物在VD13中的表达是必需的,并且在更靠前的γ-氨基丁酸能神经元中异位表达该基因会诱导标记物的表达。这些结果表明,在γ-氨基丁酸能特化之后,该基因是VD13的终末选择因子。