Differential expression of proliferative, cytoskeletal, and adhesive proteins during postnatal development of the hamster submandibular gland.

Although the submandibular gland (SMG) plays important exocrine and endocrine roles, little is known about the molecular details underlying its development. Previously, we reported that in the postnatally developing hamster SMG, GPT, the protein product of the first N-glycosylation gene, ALG7, was an in vivo marker for salivary cell proliferation. Here we investigated the proliferative, cytoskeletal, and adhesive changes during SMG postnatal development. The cellular localization and abundance of GPT, filamentous actin, and beta1 integrin receptor were examined using confocal microscopy and immunoblotting. In neonatal glands, high GPT levels marked extensive cell proliferation throughout the tissue. The apical regions of immature salivary cells displayed intense actin staining, while most of the beta1 integrin was diffusely distributed throughout the tissue. As development proceeded, discrete regions of the gland expressed attenuated levels of GPT, an increased organization of actin to the cell cortex, and beta1 integrin to the basal lamina. In the adult SMG, differentiated salivary cells displayed low levels of GPT and actin. While the abundance of beta1 integrin remained unchanged throughout development, in the adult, it was found exclusively in regions where cells contact the basal lamina. These data indicate that SMG development entails regionalized cell proliferation and polarization, and that these processes are temporally and spatially coordinated with the establishment of stable cell-substratum interactions.

ALG gene expression and cell cycle progression.

The evolutionarily conserved ALG genes function in the dolichol pathway in the synthesis of the lipid-linked oligosaccharide precursor for protein N-glycosylation. Increasing evidence suggests a role for these genes in the cell cycle. In Saccharomyces cerevisiae, coordinate regulation of the ALG genes makes up the primary genomic response to growth stimulation; several features of the ALG genes' expression resemble mammalian early growth response genes. However, only the first gene in the pathway, ALG7, is downregulated in response to an antimitogenic signal that leads to cell cycle arrest and differentiation, suggesting that selective inhibition of the first gene may be sufficient to regulate the dolichol pathway for the withdrawal from the cell cycle. The availability of mutants in the early essential ALG genes has established functional relationships between these genes' expression and G1/S transition, budding, progression through G2 and withdrawal from the cell cycle. Analysis of the regulation of ALG7 has provided insights into how this gene's expression is controlled at the molecular level. Recent studies have also begun to reveal how ALG7 expression is linked to cell cycle arrest in response to antimitogenic cues and have identified G1 cyclins as some of its downstream targets. Since the functions of the ALG genes appear to be as conserved among eukaryotes as the cell cycle machinery, it is likely that these genes play a similar role in mammalian cell proliferation and differentiation.