Rogers Crystal D, Sorrells Lisa K, Bronner Marianne E
Department of Biology, California State University, Northridge, Northridge, CA 91330, United States of America.
Division of Biology and Biological Engineering 139-74, California Institute of Technology, Pasadena, CA 91125, United States of America.
Mech Dev. 2018 Aug;152:44-56. doi: 10.1016/j.mod.2018.07.003. Epub 2018 Jul 14.
Characterizing endogenous protein expression, interaction and function, this study identifies in vivo interactions and competitive balance between N-cadherin and E-cadherin in developing avian (Gallus gallus) neural and neural crest cells. Numerous cadherin proteins, including neural cadherin (Ncad) and epithelial cadherin (Ecad), are expressed in the developing neural plate as well as in neural crest cells as they delaminate from the newly closed neural tube. To clarify independent or coordinate function during development, we examined their expression in the cranial region. The results revealed surprising overlap and distinct localization of Ecad and Ncad in the neural tube. Using a proximity ligation assay and co-immunoprecipitation, we found that Ncad and Ecad formed heterotypic complexes in the developing neural tube, and that modulation of Ncad levels led to reciprocal gain or reduction of Ecad protein, which then alters ectodermal cell fate. Here, we demonstrate that the balance of Ecad and Ncad is dependent upon the availability of β-catenin proteins, and that alteration of either classical cadherin modifies the proportions of the neural crest and neuroectodermal cells that are specified.
本研究通过表征内源性蛋白质的表达、相互作用和功能,确定了发育中的禽类(原鸡)神经细胞和神经嵴细胞中N-钙黏蛋白和E-钙黏蛋白之间的体内相互作用及竞争平衡。许多钙黏蛋白,包括神经钙黏蛋白(Ncad)和上皮钙黏蛋白(Ecad),在发育中的神经板以及从新闭合的神经管分层的神经嵴细胞中表达。为了阐明其在发育过程中的独立或协同功能,我们检测了它们在颅区的表达。结果显示Ecad和Ncad在神经管中有惊人的重叠和不同的定位。使用邻近连接分析和免疫共沉淀,我们发现Ncad和Ecad在发育中的神经管中形成异型复合物,并且Ncad水平的调节导致Ecad蛋白的相互增加或减少,进而改变外胚层细胞命运。在此,我们证明Ecad和Ncad的平衡取决于β-连环蛋白的可用性,并且任一经典钙黏蛋白的改变都会改变特定的神经嵴细胞和神经外胚层细胞的比例。