Bombesin receptor gene expression during mammalian development.

Mammalian bombesin-like peptides (gastrin-releasing peptide [GRP] and neuromedin B [NMB]) and their receptors (GRP-R and NMB-R) can stimulate growth of cultured cells, and have been shown to be part of an autocrine growth regulatory network in some human small cell lung carcinoma cells. Given the connection between bombesin receptor expression and bombesin-mediated growth regulation in cultured cells, we were interested in investigating the possibility that bombesin peptides and their receptors might be important for normal growth and differentiation during development. As a first step, we examined the distribution of expression of GRP-R and NMB-R mRNA during rat embryonic development to identify changing spatio-temporal patterns of gene expression. In situ hybridization studies show that GRP-R mRNA is expressed at early embryonic stages in various locations of the nervous, urogenital, respiratory, and gastrointestinal systems. In contrast, the distribution of expression of NMB-R mRNA is more limited (upper gastrointestinal tract, bladder, and central nervous system) and is observed at later embryonic stages. In most locations, receptor mRNA levels increased steadily throughout development after onset of expression. However, transient GRP-R mRNA expression is observed in the posterior pituitary where expression increases from embryonic day 12 to 20, and abruptly disappears at birth. These studies suggest that appropriate development of several organ systems, in particular the posterior pituitary, may involve GRP-R-mediated signaling. We plan to test this hypothesis using gene targeting to inactivate the GRP-R gene in the mouse.