Dataset Information

Regulation of N-glycolylneuraminic acid biosynthesis in developing pig small intestine.

ABSTRACT: N -Glycolylneuraminic acid (Neu5Gc), an abundant sialic acid in animal glycoconjugates, is formed by the enzyme CMP-N-acetylneuraminic acid (CMP-Neu5Ac) hydroxylase. The amount of Neu5Gc relative to other sialic acids is highly dependent on the species, tissue and developmental stage. Although the activity of the hydroxylase is a key factor in controlling Neu5Gc incorporation in adult animals, little is known about the regulation of hydroxylase expression and the role of this enzyme in determining changes in Neu5Gc during development. Using pig small intestine as a model system, the appearance of total sialic acid and the regulation of Neu5Gc biosynthesis during development were studied in various regions of this tissue. The amount of total sialic acid and Neu5Gc declined markedly in 2 weeks after birth. Although in subsequent developmental phases there were no positional differences in total sialic acid, a significant proximal-to-distal increase in Neu5Gc was detected. In all cases, a good correlation between the amount of Neu5Gc, the activity of the hydroxylase and the level of hydroxylase mRNA was observed. However, Western-blot analysis revealed considerable accumulation of less active enzyme in the post partum period, which persisted until adulthood. No evidence for cytosolic factors influencing the hydroxylase activity or for the formation of truncated enzyme was found, raising the possibility that other regulatory mechanisms are involved. The relevance of these results in the formation of Neu5Gc as a receptor for certain pig enteric pathogens is also discussed.

SUBMITTER: Malykh YN

PROVIDER: S-EPMC1223197 | biostudies-other | 2003 Mar

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Studies of adult mice lacking either GATA4 or GATA6 in the small intestine demonstrate roles for these factors in small intestinal biology. Deletion of Gata4 in the adult mouse intestine revealed an essential role for GATA4 in jejunal function. Deletion of Gata6 in the adult mouse ileum alters epithelial cell types and ileal enterocyte gene expression. The effect of deletion of Gata4 or Gata6 alone during embryonic small intestinal development, however, has not been examined. We recently demonstrated that loss of both factors in double conditional knockout embryos causes severe defects in jejunal development. Therefore, the goal of this study is to provide phenotypic analysis of the small intestine of single Gata4 and Gata6 conditional knockout embryos.Villin-Cre was used to delete Gata4 or Gata6 in the developing intestinal epithelium. Elimination of either GATA4 or GATA6 in the jejunum, where these factors are co-expressed, caused changes in enterocyte and enteroendocrine cell gene expression. Ectopic expression of markers of the ileal-specific bile acid metabolism pathway was induced in GATA4-deficient jejunum but not in GATA6-deficient jejunum. A subtle increase in goblet cells was also identified in jejunum of both mutants. In GATA6-deficient embryonic ileum, villus length was altered, and enterocyte gene expression was perturbed including ectopic expression of the colon marker Car1. Goblet cells were increased, and enteroendocrine cells were decreased.Overall, we show that aspects of the phenotypes observed in the small intestine of adult Gata4 and Gata6 conditional knockout mice emerge during development. The effect of eliminating GATA6 from the developing ileum was greater than that of eliminating either GATA4 or GATA6 from the developing jejunum likely reflecting functional redundancy between these factors in the jejunum. Although GATA4 and GATA6 functions overlap, our data also suggest unique functions for GATA4 and GATA6 within the developing intestine. GATA4 likely operates independently of GATA6 within the jejunum to regulate jejunal versus ileal enterocyte identity and consequently jejunal physiology. GATA6 likely regulates enteroendocrine cell differentiation cell autonomously whereas GATA4 affects this population indirectly.

Dataset Information

Regulation of N-glycolylneuraminic acid biosynthesis in developing pig small intestine.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets