Pruitt S C
Roswell Park Cancer Institute, Department of Molecular and Cellular Biology, Buffalo, NY 14263.
Development. 1994 Nov;120(11):3301-12. doi: 10.1242/dev.120.11.3301.
Endogenous signals capable of inducing neuroectodermal differentiation are expressed by differentiating P19 EC cells in vitro. The present study demonstrates that at least two discrete signals are required. One is expressed by isolated primitive streak mesoderm-like cell lines and has the capacity to induce the expression of Pax-3 but, alone, induces neural differentiation inefficiently. The second signal is not expressed by the primitive streak mesoderm-like cell line but is present in conditioned media from differentiating P19 EC cells following DMSO treatment. This signal does not induce either Pax-3 expression or morphological differentiation and does not commit stem cells to a neuroectodermal fate. Rather, it acts synergistically with the signal derived from the primitive streak mesoderm-like cells to increase the efficiency with which stem cells respond initially by Pax-3 expression and subsequently by differentiation towards neural lineages. The activity of this second signal can be replaced by forskolin and 3-isobutyl-1-methyl-xanthine suggesting that its effects are transduced by a cyclic nucleotide-dependent pathway.
能够诱导神经外胚层分化的内源性信号在体外分化的P19 EC细胞中表达。本研究表明，至少需要两种不同的信号。一种由分离的原条中胚层样细胞系表达，具有诱导Pax - 3表达的能力，但单独作用时诱导神经分化的效率较低。第二种信号不是由原条中胚层样细胞系表达的，而是存在于经二甲基亚砜（DMSO）处理后分化的P19 EC细胞的条件培养基中。这种信号既不诱导Pax - 3表达，也不诱导形态分化，也不会使干细胞定向分化为神经外胚层命运。相反，它与来自原条中胚层样细胞的信号协同作用，提高干细胞最初通过Pax - 3表达以及随后向神经谱系分化的反应效率。第二种信号的活性可以被福斯可林和3 - 异丁基 - 1 - 甲基黄嘌呤替代，这表明其作用是通过环核苷酸依赖性途径转导的。
