Project description:Molecular adaptation of the intestinal mucosa occurs during microbial conventionalization to maintain a balanced immune response. However, the genetic regulation of such adaptation is obscure. Here, combined analysis of germ free and conventionalized mice revealed that the major molecular adaptations were initiated at day 4 of conventionalization with a strong induction of innate immune functions followed by stimulation of adaptive immune functions. We identified central regulatory genes and reconstructed a common regulatory network that appeared to be sufficient to regulate the dynamic adaptation of the intestinal mucosa to the colonizing microbiota. The majority of the genes within this regulatory network play roles in mucosal inflammatory diseases in mouse and human. We propose that the identified central regulatory network may serve as a genetic signature for control of intestinal homeostasis in healthy mice and may help to unravel the genetic basis of pathway dysregulation in human intestinal inflammatory diseases. Expression profiling of jejunum, ileum, and colon tissue from germ-free and colonized mice at day 1,2,4,8,16 and 30.
Project description:Resident microorganisms (microbiota) have far-reaching effects on the biology of their animal hosts, with major consequences for the host’s health and fitness. Some of these effects can be explained by microbial impacts on the expression of individual genes but a full understanding of microbiota-dependent gene regulation requires analysis of the overall architecture of the host transcriptome. In this study, we investigated the impact of the microbiota on the global structure of the transcriptome of Drosophila. Our transcriptomic analysis of 17 Drosophila lines representative of the global genetic diversity of this species yielded a total of 11 transcriptional modules of co-expressed genes. For 7 of these modules, the strength of the transcriptional network (defined as gene-gene coexpression) differed significantly between flies bearing a defined gut microbiota (gnotobiotic flies) and flies reared under microbiologically-sterile conditions (axenic flies). Furthermore, the network structure was uniformly stronger in these microbiota-dependent modules than in both the microbiota-independent modules in gnotobiotic flies and all modules in axenic flies, indicating that the presence of the microbiota tightens gene regulation in a subset of the transcriptome. The genes constituting the microbiota-dependent transcriptional modules include regulators of growth, metabolism and neurophysiology, previously implicated in mediating phenotypic effects of microbiota on Drosophila phenotype. Together these results provide the key first evidence that the microbiota strengthens the co-expression of genesin specific networks of functionally-related transcripts relative to the animal’s intrinsic baseline level of co-expression. Our system-wide analysis demonstrates that the presence of microbiota enhances the structure of the transcriptional network in the animal host. This finding has potentially major implications for understanding of the mechanisms by which microbiota affect host health and fitness, and the ways in which hosts and their resident microbiota coevolve.
Project description:The final size of plant organs such as leaves is tightly controlled by environmental and genetic factors that must spatially and temporally coordinate cell expansion and cell cycle activity. However this regulation of organ growth is still poorly understood. The aim of this study is to gain more insight in the genetic control of leaf size in Arabidopsis by performing a comparative analysis of transgenic lines that produce larger leaves under standardized environmental conditions. To this end, we selected five genes, belonging to different functional classes, that all positively affect leaf size when over-expressed: AVP1, GRF5, JAW, BRI1 and GA20OX1. We show that the increase in leaf area in these lines depends on leaf position and growth conditions and that all five lines affect leaf size differently. However, in all cases an increase in cell number is, entirely or predominantly, responsible for the leaf size enlargement. By means of analyses of hormone levels, transcriptome and metabolome we provide deeper insight in the molecular basis of the growth phenotype for the individual lines. A comparative analysis between them indicates that enhanced organ growth is governed by different, seemingly independent pathways. The analysis of transgenic lines simultaneously over-expressing two growth-enhancing genes further supports the concept that multiple pathways independently converge on organ size control in Arabidopsis.