Xie Jing, Wang Wei-Qing, Liu Ting-Xi, Deng Min, Ning Guang
School of Medicine, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Disease, Shanghai Jiaotong University, Shanghai, People's Republic of China.
J Endocrinol. 2008 Sep;198(3):451-8. doi: 10.1677/JOE-08-0221. Epub 2008 Jun 27.
Chromogranin A (CHGA), a protein participating in the biogenesis of dense core secretory granules in various neuroendocrine tissues, plays a critical role in the release of hormones/peptides and the pathogenesis of pheochromocytoma. However, little is known about the developmental origin of CHGA-expressing cells during embryogenesis. Here, we report the structural characterization and spatio-temporal expression pattern of zebrafish (Danio rerio) ortholog of mammalian CHGA. The earliest expression of chga transcripts was observed at 16 h post fertilization in the developing cranial ganglia as six distinct cellular masses arranged bilaterally as strings of beads in the dorsal root ganglia (DRG) precursors along the dorsal trunk. With development advancing, the chga transcripts were expressed abundantly in diencephalon, mesencephalon, and rhombencephalon as well as in the DRG. Interestingly, double in situ hybridization assay of chga with genes expressed in pronephros (Wilms' tumor suppressor 1, wt1), adrenal cortex (side-chain cleavage enzyme, scc), and sympathoadrenal neuron/chromaffin cell (dopamine-beta-hydroxylase, dbh), respectively, showed that the chga-expressing cells are spatially separated from wt1-, scc-, and dbh-positive cell populations during early embryonic development. The pronephros region does not express chga even up to 7 days post fertilization, while chga positive-staining cells bind in the brain and DRG, indicating that chga may play an important role in nervous system development during the early embryonic stages.
嗜铬粒蛋白A(CHGA)是一种参与多种神经内分泌组织中致密核心分泌颗粒生物合成的蛋白质,在激素/肽的释放以及嗜铬细胞瘤的发病机制中起关键作用。然而,关于胚胎发育过程中表达CHGA的细胞的发育起源知之甚少。在此,我们报告了哺乳动物CHGA的斑马鱼直系同源物的结构特征和时空表达模式。在受精后16小时,在发育中的颅神经节中观察到最早的chga转录本表达,表现为六个不同的细胞团,沿背侧躯干在背根神经节(DRG)前体中双侧排列成串珠状。随着发育的推进,chga转录本在间脑、中脑、后脑以及DRG中大量表达。有趣的是,分别将chga与在原肾(威尔姆斯肿瘤抑制因子1,wt1)、肾上腺皮质(侧链裂解酶,scc)和交感肾上腺神经元/嗜铬细胞(多巴胺-β-羟化酶,dbh)中表达的基因进行双重原位杂交分析,结果显示在胚胎早期发育过程中,表达chga的细胞在空间上与wt1、scc和dbh阳性细胞群体分离。即使在受精后7天,原肾区域也不表达chga,而chga阳性染色细胞在脑和DRG中出现,这表明chga可能在胚胎早期阶段的神经系统发育中起重要作用。