Morell M, Tsan Yao-chang, O'Shea K Sue
Centro Pfizer de Genomica e Investigacion Oncologica, Universidad de Granada, Junta de Andalucia, Parque Tecnologico Ciencias de la Salud, Avda de la Ilustracion, 114 18007, Granada Spain.
Department of Cell and Developmental Biology, School of Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Stem Cell Res. 2015 Jan;14(1):79-94. doi: 10.1016/j.scr.2014.11.001. Epub 2014 Nov 22.
Multipotent, self-renewing stem cells are present throughout the developing nervous system remaining in discrete regions of the adult brain. In the subventricular zone (SVZ) signaling molecules, including the bone morphogenetic proteins and their secreted inhibitor, noggin appear to play a critical role in controlling neural stem cell (NSC) behavior. To examine the function of this signaling pathway in the intact nervous system, we developed a transgenic mouse model in which noggin expression can be induced specifically in NSC via a nestin-driven reverse tetracycline-controlled transactivator (rtTA). In adult animals, the induction of noggin expression promotes the proliferation of neural progenitors in the SVZ, and shifts the differentiation of B cells (NSC) from mature astrocytes to transit amplifying C cells and oligodendrocyte precursor cells without depleting the NSC population. Noggin expression significantly increases neuronal and oligodendrocyte differentiation both in vivo and in vitro when NSCs are grown as neurospheres. These results demonstrate that noggin/BMP interactions tightly control cell fate in the SVZ.
多能性、自我更新的干细胞存在于整个发育中的神经系统中，并留存于成体大脑的离散区域。在脑室下区（SVZ），包括骨形态发生蛋白及其分泌抑制剂头蛋白在内的信号分子似乎在控制神经干细胞（NSC）行为方面发挥着关键作用。为了研究该信号通路在完整神经系统中的功能，我们构建了一种转基因小鼠模型，其中头蛋白的表达可通过巢蛋白驱动的反向四环素调控反式激活因子（rtTA）在神经干细胞中特异性诱导。在成年动物中，头蛋白表达的诱导促进了脑室下区神经祖细胞的增殖，并使B细胞（神经干细胞）的分化从成熟星形胶质细胞转变为过渡放大C细胞和少突胶质细胞前体细胞，而不会耗尽神经干细胞群体。当神经干细胞作为神经球生长时，头蛋白表达在体内和体外均显著增加神经元和少突胶质细胞的分化。这些结果表明，头蛋白/骨形态发生蛋白相互作用紧密控制着脑室下区的细胞命运。
