McCauley Brenna S, Akyar Eda, Saad H Rosa, Hinman Veronica F
Department of Biological Sciences, Carnegie Mellon University, 4400 5th Ave, Pittsburgh, PA 15213, USA.
Department of Biological Sciences, Carnegie Mellon University, 4400 5th Ave, Pittsburgh, PA 15213, USA
Development. 2015 Jan 1;142(1):207-17. doi: 10.1242/dev.113043.
In many invertebrates, the nuclearization of β-catenin at one pole of the embryo initiates endomesoderm specification. An intriguing possibility is that a gradient of nuclear β-catenin (nβ-catenin), similar to that operating in vertebrate neural tube patterning, functions to distinguish cell fates in invertebrates. To test this hypothesis, we determined the function of nβ-catenin during the early development of the sea star, which undergoes a basal deuterostomal mode of embryogenesis. We show that low levels of nβ-catenin activity initiate bra, which is expressed in the future posterior endoderm-fated territory; intermediate levels are required for expression of foxa and gata4/5/6, which are later restricted to the endoderm; and activation of ets1 and erg in the mesoderm-fated territory requires the highest nβ-catenin activity. Transcription factors acting downstream of high nβ-catenin segregate the endoderm/mesoderm boundary, which is further reinforced by Delta/Notch signaling. Significantly, therefore, in sea stars, endomesoderm segregation arises through transcriptional responses to levels of nβ-catenin activity. Here, we describe the first empirical evidence of a dose-dependent response to a dynamic spatiotemporal nβ-catenin activity that patterns cell fates along the primary axis in an invertebrate.
在许多无脊椎动物中，β-连环蛋白在胚胎的一极发生核化，从而启动内胚层和中胚层的特化。一种有趣的可能性是，核β-连环蛋白（nβ-连环蛋白）的梯度，类似于在脊椎动物神经管模式形成中起作用的梯度，在无脊椎动物中发挥区分细胞命运的功能。为了验证这一假设，我们确定了nβ-连环蛋白在海星早期发育过程中的功能，海星经历了一种基础的后口动物胚胎发生模式。我们发现，低水平的nβ-连环蛋白活性启动bra的表达，bra在未来注定形成后端内胚层的区域表达；中等水平的nβ-连环蛋白活性是foxa和gata4/5/6表达所必需的，它们随后局限于内胚层；而在注定形成中胚层的区域中ets1和erg的激活需要最高水平的nβ-连环蛋白活性。高nβ-连环蛋白下游的转录因子分隔内胚层/中胚层边界，Delta/Notch信号进一步加强了这一边界。因此，在海星中，内胚层和中胚层的分离是通过对nβ-连环蛋白活性水平的转录反应产生的。在这里，我们描述了第一个关于对动态时空nβ-连环蛋白活性的剂量依赖性反应的实证证据，这种反应在无脊椎动物中沿着主轴决定细胞命运。
