Project description:Understanding congenital liver disease requires elucidation of the signaling pathways and transcriptional events in the developing liver. Comprehensive assessment of gene expression between 10.5 and 16.5 dpc in the developing mouse liver and comparison with adult liver and non-hepatic embryonic tissue was validated with real-time PCR and in situ hybridization. The broad nature of the analysis provides insights into patterns of genetic control of hepatogenesis. Pathways implicated in human disease are highly regulated at the transcriptional level. Rather than activating or inhibiting a pathway or biological process by altering the expression of a single signaling molecule, transcriptional changes in large numbers of genes in a pathway or process are regulated in a coordinated manner. For example, both TGF-beta and Notch signaling is inhibited during hepatogenesis not just by decreasing transcription of multiple pathway members, but also with a complementary increase in the transcription of a pathway inhibitor. Similarly, genes related to specific biological processes exhibit strong temporal synchronization in which multiple members of the pathway have similar transcriptional regulation over time. Global coordination of signaling or functional families at the transcriptional level may be a mechanism to produce robustness of the desired outcomes. In addition, this comprehensive analysis provides a database for the further study of transcriptional events during liver development by identifying liver-specific, highly regulated genes. Experiment Overall Design: In order to provide transcriptional profile of the developing liver compared both to normal adult liver and non-hepatic embryonic tissueswe performed high-density microarray analysis using Affymetrix MG 430 2.0 chips for embryonic liver samples at 10.5, 11.5, 12.5, 13.5, 14.5, and 16.5 days post conception (dpc), embryo-minus liver tissues at 10.5, 11.5, 12.5, and 14.5 dpc, and normal 10-week-old adult mouse liver. Each sample consisted of at least five embryos.

Project description:Pacific salmon undergo dramatic physiological remodeling during their terminal spawning migration, culminating in reproductive maturation, senescence, and death. To investigate the molecular mechanisms underlying these processes, we characterized transcriptomic changes in wild pink salmon (Oncorhynchus gorbuscha) sampled at three migratory stages (marine, riverine, and spawning ground) and across three tissues central to endocrine regulation and energy metabolism: gonads, head kidney, and skeletal muscle. RNA sequencing and dDifferential gene expression analyses waswere performed to identify biological pathways associated with maturation and semelparity. Transcriptomic changesremodeling wereas most pronounced during the final transition from river migrating fish entry to spawning, with the gonads exhibiting the greatest number of differentially expressed genes, followed by skeletal muscle and head kidney. Gene ontology analyses revealed coordinated upregulation of pathways associated with starvation responses, lipid mobilization, tissue catabolism, proteolysis, autophagy, and cell death across tissues. Immune and inflammatory processes were elevated in skeletal muscle and head kidney, while gonads showed strong enrichment of insulin signaling, steroid metabolism, and hormone-response pathways. Analysis of endocrine receptor expression identified tissue-specific and ohnolog-specific regulation of receptors involved in thyroid, growth hormone, insulin, gonadotropin, sex steroid, and glucocorticoid signaling, suggesting functional divergence among duplicated salmonid genes. These findings identified in pink salmon provide evidence that the demonstrate that the most extreme physiological changes occur extensive molecular reprogramming in pink salmon occurs duringat the time of final maturation rather than freshwater entry. The coordinated activation of endocrine, metabolic, and degenerative pathways supports a mechanistic link between reproductive development and semelparous senescence, providing new insight into the endocrine and transcriptomic networks that govern spawning-associated physiological decline in Pacific salmon.

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Mus musculus

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