Laboratory of Neurochemistry, NINDS, NIH, Bethesda, Maryland 20892; and Laboratory of Biological Chemistry, DTP, DCT, NCI, Bethesda, Maryland 20892.
Mol Cell Neurosci. 1993 Feb;4(1):13-24. doi: 10.1006/mcne.1993.1002.
Bombesin-like peptides can stimulate growth of cultured cells derived from ectoderm, endoderm, or mesenchyme and act as autocrine growth factors in some lung carcinoma cell lines. Recently, cDNA clones for two mammalian bombesin receptors (BN-R), gastrin-releasing peptide receptor (GRP-R) and neuromedin B receptor (NMB-R), were characterized and shown to be present in distinct regions of the central nervous system at birth. To determine whether the spatial and/or temporal expression of BN-R genes correlated with tissue-specific or organ-specific developmental events, the prenatal distribution of GRP-R and NMB-R mRNAs were compared by in situ hybridization histochemistry. The differential expression of these two BN-R genes was striking. From early embryonic stages, GRP-R mRNA was expressed in various organs, including nervous, urogenital, respiratory, and digestive systems. In contrast, NMB-R gene expression was detected at later embryonic stages and the distribution of expression was much more limited. In most tissues, after onset of expression, both receptor mRNAs showed a steady increase in expression throughout development. However, transient expression of GRP-R mRNA was seen in the posterior pituitary. Intense GRP-R labeling of posterior pituitary cells was seen from E12 to E20, but at birth, GRP-R mRNA levels were undetectable. These results suggest that (a) two BN-R subtypes mediate independent functions during development, (b) ontogenesis of multiple organs may involve GRP-R mediated events, and (c) GRP-R gene expression is involved in differentiation/development of the pituitary gland.
铃蟾肽样肽可刺激外胚层、内胚层或中胚层来源的培养细胞生长,并在一些肺癌细胞系中作为自分泌生长因子发挥作用。最近,两种哺乳动物铃蟾肽受体(BN-R)、胃泌素释放肽受体(GRP-R)和神经介素 B 受体(NMB-R)的 cDNA 克隆被鉴定出来,并在出生时存在于中枢神经系统的不同区域。为了确定 BN-R 基因的空间和/或时间表达是否与组织特异性或器官特异性发育事件相关,通过原位杂交组织化学比较了 GRP-R 和 NMB-R mRNA 的产前分布。这两种 BN-R 基因的差异表达非常显著。从早期胚胎阶段开始,GRP-R mRNA 就存在于各种器官中,包括神经系统、泌尿生殖系统、呼吸系统和消化系统。相比之下,NMB-R 基因的表达在胚胎后期才被检测到,而且表达的分布范围要窄得多。在大多数组织中,表达开始后,两种受体 mRNA 的表达都在整个发育过程中稳步增加。然而,在后垂体中观察到 GRP-R mRNA 的短暂表达。从 E12 到 E20 可以看到后垂体细胞中强烈的 GRP-R 标记,但在出生时,GRP-R mRNA 水平无法检测到。这些结果表明:(a) 两种 BN-R 亚型在发育过程中介导独立的功能;(b) 多个器官的发生可能涉及 GRP-R 介导的事件;(c) GRP-R 基因表达参与了垂体的分化/发育。