Kim M J, Han J K
Department of Life Science, Pohang University of Science and Technology, San 31 Hyoja-Dong, Pohang, Kyungbuk, South Korea.
Mech Dev. 1999 Dec;89(1-2):55-64. doi: 10.1016/s0925-4773(99)00197-5.
The cAMP signaling system has been postulated to be involved in embryogenesis of many animal species, however, little is known about its role in embryonic axis formation in vertebrates. In this study, the role of the cAMP signaling pathway in patterning the body plan of the Xenopus embryo was investigated by expressing and activating the exogenous human 5-hydroxytryptamine type 1a receptor (5-HT(1a)R) which inhibits adenylyl cyclase through inhibitory G-protein in embryos in a spatially- and temporally-controlled manner. In embryos, ventral, but not dorsal expression and stimulation of this receptor during blastula and gastrula stages induced secondary axes but were lacking anterior structures. At the molecular level, 5-HT(1a)R stimulation induced expression of the dorsal mesoderm marker genes, and downregulated expression of the ventral markers but had no effect on expression of the pan mesodermal marker gene in ventral marginal zone explants. In addition, ventral expression and stimulation of the receptor partially restored dorsal axis of UV-irradiated axis deficient embryo. Finally, the total mass of cAMP differs between dorsal and ventral regions of blastula and gastrula embryos and this is regulated in a temporally-specific manner. These results suggest that the cAMP signaling system may be involved in the transduction of ventral signals in patterning early embryos.
环磷酸腺苷(cAMP)信号系统被推测参与了许多动物物种的胚胎发育过程,然而,关于其在脊椎动物胚胎轴形成中的作用却知之甚少。在本研究中,通过以时空可控的方式在胚胎中表达并激活外源性人类5-羟色胺1a型受体(5-HT(1a)R)来研究cAMP信号通路在非洲爪蟾胚胎体轴模式形成中的作用,该受体通过抑制性G蛋白抑制腺苷酸环化酶。在胚胎中,囊胚期和原肠胚期腹侧而非背侧表达并刺激该受体可诱导形成次生轴,但缺乏前部结构。在分子水平上,5-HT(1a)R刺激诱导背侧中胚层标记基因的表达,并下调腹侧标记基因的表达,但对腹侧边缘区外植体中泛中胚层标记基因的表达没有影响。此外,受体的腹侧表达和刺激部分恢复了紫外线照射导致轴缺陷胚胎的背轴。最后,囊胚期和原肠胚期胚胎的背侧和腹侧区域之间的cAMP总量不同,且这是以时间特异性方式调控的。这些结果表明,cAMP信号系统可能参与了早期胚胎模式形成中腹侧信号的转导。