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Relationships between polydnavirus genomes and viral gene expression.

Polydnavirus genomes and viral gene functions are atypical for viruses. Polydnaviruses are the only group of viruses with segmented DNA genomes and have an unusual obligate mutualistic association with parasitic Hymenoptera, in which the virus is required for survival of the wasp host and vice versa. The virus replicates asymptomatically in the wasp host but severely disrupts lepidopteran host physiology in the absence of viral DNA replication. It is not surprising then that viral gene expression is divergent in its two insect hosts and that differences in viral gene expression are linked to these divergent functions. Some viral genes are expressed only in the wasp host while other viral genes are expressed only in the lepidopteran host and are presumed to be involved in the disruption of host physiological systems. Our laboratory has described the expression and regulation of a family of viral genes implicated in suppressing the lepidopteran immune system, the cys-motif genes. In conjunction with these studies we have described the physical organization of additional viral gene segments. We have cloned, mapped and begun the sequence analysis of selected viral DNA segments. We have noted that some viral DNA segments are nested and that nested viral DNA segments encode the abundantly expressed, secreted cys-motif genes. Conversely, other viral segments are not nested, encode less abundantly expressed genes and may be targeted intra-cellularly. These results suggest that nesting of segments in polydnavirus genomes may be linked to the levels of gene expression. By extension, the unique, segmented organization of polydnavirus genomes may be associated, in part, with the requirement for divergent levels of viral gene expression in lepidopteran hosts in the absence of viral DNA replication.

Journal Article↗

The Epstein-Barr virus EBNA-LP protein preferentially coactivates EBNA2-mediated stimulation of latent membrane proteins expressed from the viral divergent promoter.

The mechanistic contribution of the Epstein-Barr virus (EBV) EBNA-LP protein to B-cell immortalization remains an enigma. However, previous studies have indicated that EBNA-LP may contribute to immortalization by enhancing EBNA2-mediated transcriptional activation of the LMP-1 gene. To gain further insight into the potential role EBNA-LP has in EBV-mediated B-cell immortalization, we asked whether it is a global or gene-specific coactivator of EBNA2 and whether coactivation requires interaction between these proteins. In type I Burkitt's lymphoma cells, we found that EBNA-LP strongly coactivated EBNA2 stimulation of LMP-1 and LMP2B RNAs, which are expressed from the viral divergent promoter. Surprisingly, the viral LMP2A gene and cellular CD21 and Hes-1 genes were induced by EBNA2 but showed no further induction after EBNA-LP coexpression. We also found that EBNA-LP did not stably interact with EBNA2 in coimmunoprecipitation assays, even though the conditions were adequate to observe specific interactions between EBNA2 and its cellular cofactor, CBF1. Colocalization between EBNA2 and EBNA-LP was not detectable in EBV-transformed cell lines or transfected type I Burkitt's cells. Finally, no significant interactions between EBNA2 and EBNA-LP were found with mammalian two-hybrid assays. From this data, we conclude that EBNA-LP is not a global coactivator of EBNA2 targets, but it preferentially coactivates EBNA2 stimulation of the viral divergent promoter. While this may require specific transient interactions between these proteins that only occur in the context of the divergent promoter, our data strongly suggest that EBNA-LP also cooperates with EBNA2 through mechanisms that do not require direct or indirect complex formation between these proteins.

B-Lymphocytes↗

Rice calcium-dependent protein kinase isoforms OsCDPK2 and OsCDPK11 show different responses to light and different expression patterns during seed development.

We investigated the spatial and temporal expression patterns of two rice calcium-dependent protein kinases (CDPKs), OsCDPK2 and OSCDPK11, using isoform-specific antisera. Bands of the expected molecular sizes for OsCDPK2 (59 kDa) and OsCDPK11 (61 kDa) were detected on western blots. OsCDPK2 and OsCDPK11 mRNA and protein levels increased in unison during flower development. However, at the onset of seed development, the protein expression profiles diverged significantly. OsCDPK2 protein was expressed at low levels during early seed development, but increased to high levels that were maintained in later stages (20 days after fertilisation, DAF). Conversely, OsCDPK11 protein levels were high at the beginning of seed development, but fell rapidly from 10 DAF onwards. This decrease in the level of OsCDPK11 protein was associated with the abundant synthesis of a truncated mRNA species. OsCDPK2 expression was also closely associated with light perception. OsCDPK2 protein was barely detectable in green leaves exposed to light, but levels increased sharply when plants were shifted to darkness. Initially, this increase reflected a rapid elevation in the levels of OsCDPK2 mRNA, which was normally located in the mesophyll. Conversely, OsCDPK11 mRNA and protein levels were unaffected by light. These data strongly indicate that two rice CDPK isoforms have different functions in seed development and in response to light in leaves.

Blotting, Western↗

Position-specific activity of the Hox1.1 promoter in transgenic mice.

During development, positional values have to be assigned to groups of cells. The murine Hox genes are a class of genes that are predicted to be involved at some stage in this process. During embryogenesis they are expressed in distinct overlapping region- and stage-specific patterns and therefore must be regulated in response to positional information. In this study, we have analysed the activity of Hox1.1 promoter sequences in transgenic mice. The use of lacZ as a marker allows a detailed analysis of expression at the single cell level during early embryonic development. We show that 3.6 kbp of promoter and 1.7 kbp of 3' sequences provide sufficient regulatory information to express a transgene in a spatial and temporal manner indistinguishable from the endogenous Hox1.1 gene during the period of development when Hox1.1 expression is established. The activation occurs in a strict order in specific ectodermal and mesodermal domains. Within each of these domains the transgene is activated over a period of four hours apparently randomly in single cells. In a following second period, Hox1.1 and transgene expression patterns diverge. In this period, transgene expression persists in many mesodermally derived cells that do not express Hox1.1 indicating the absence of a negative regulatory element in the transgene. The anterior boundary of transgene expression is identical to that of Hox1.1. However, no posterior boundary of transgene expression is set, suggesting that a separate element absent from the transgene specifies this boundary.

Animals↗

Insulin regulates expression of metabolic genes through divergent signaling pathways.

The regulation of metabolic gene expression is a major mechanism by which insulin modulates glucose homeostasis. Defective transcription factors or signal transduction molecules that are required for insulin regulated gene expression could contribute to insulin resistance. The phosphoenolpyruvate carboxykinase (PEPCK) and hexokinase II (HKII) genes are involved in metabolic processes that represent opposing facets of glucose homeostasis, namely gluconeogenesis and glucose utilization. The regulation of the PEPCK and HKII genes by insulin has been studied in great detail at the level of both transcription and signal transduction. Recent work on the insulin signaling pathways that lead to down-regulation of PEPCK gene expression and upregulation of HKII gene expression has shown that they both require activation of phosphatidylinositol 3-kinase (PI3K) for the transmission of the insulin signal. However, the pathways diverge after PI3K and lead to activation of different downstream effectors. In this paper we review the results of studies on the transcriptional regulation of these genes by insulin and the signal transduction pathways that mediate these responses.

Animals↗

A cluster of NIF transcriptional regulators with divergent patterns of spore-specific expression in Phytophthora infestans.

Seven genes encoding putative nuclear LIM interactor-interacting factors (NIFs) from Phytophthora infestans were characterized. Four exhibited spore-specific expression and clustered within 20kb, and three hyphal forms were also identified. Pi-nifS mRNA accumulated during sporulation, and Pi-nifC1, Pi-nifC2, and Pi-nifC3 mRNA during zoosporogenesis. By expressing fusions with the beta-glucuronidase reporter gene in transformants, promoter fragments determining patterns of transcription specific to sporangia formation or zoosporogenesis were identified. Such studies also indicated that Pi-nifS was expressed at a late stage of sporulation. Pi-nifC1, Pi-nifC2, and Pi-nifC3 induction involved inositol-trisphosphate signaling based on studies with 2-aminoethoxydiphenylborate and U-73122, was independent of verapamil-sensitive signals, and required the same cool temperatures that trigger zoosporogenesis. In contrast, warmer temperatures favoring direct sporangial germination caused Pi-nifS mRNA to rapidly decay, while verapamil increased mRNA levels. The divergent expression and clustering of the spore-specific genes may help reveal how genomes and developmental pathways evolved within the genus.

Amino Acid Sequence↗

Evolution of neuroblast identity: seven-up and prospero expression reveal homologous and divergent neuroblast fates in Drosophila and Schistocerca.

In the Drosophila CNS, early neuroblast formation and fate are controlled by the pair-rule class of segmentation genes. The distantly related Schistocerca (grasshopper) embryo has a similar arrangement of neuroblasts, despite lack of known pair-rule gene function. Does divergent pair-rule gene function lead to different neuroblast identities, or can different patterning mechanisms produce homologous neuroblasts? We use four molecular markers to compare Drosophila and Schistocerca neuroblast identity: seven-up, prospero, engrailed, and fushi-tarazu/Dax. In both insects some early-forming neuroblasts share key features of neuroblast identity (position, time of formation, and temporally accurate gene expression); thus, different patterning mechanisms can generate similar neuroblast fates. In contrast, several later-forming neuroblasts show species-specific differences in position and/or gene expression; these neuroblast identities seem to have diverged, suggesting that evolution of the insect central nervous system can occur through changes in embryonic neuroblast identity.

Amino Acid Sequence↗

Endocrine regulation of gender-divergent mouse organic anion-transporting polypeptide (Oatp) expression.

Several examples of gender-divergent pharmacokinetics exist in humans and experimental animals, and one reason for these variations may be gender differences in transporter expression. Organic anion transporting polypeptides (Oatp) are transporters involved in hepatic and renal uptake of many organic compounds. In mouse livers, Oatp1a1 is male-predominant, whereas Oatp1a4 is female-predominant. However, in kidneys, Oatp1a1 and Oatp3a1 are both female-predominant. The purpose of the present study was to determine whether sex hormones and/or growth hormone (GH) secretion patterns are responsible for the gender-specific Oatp expression in mice. Gonadectomized mice, GH-releasing hormone receptor-deficient little (lit/lit) mice, and hypophysectomized mice were used with replacement of sex hormones or GH in male or female secretion patterns. Androgens increased Oatp1a1 mRNA in liver and kidney, whereas male-pattern GH administration increased Oatp1a1 mRNA in livers but not in kidneys. Hepatic Oatp1a4 mRNA levels were decreased by both androgens and male-pattern GH administration. In kidneys, Oatp3a1 mRNA expression was only induced by androgen treatment. In conclusion, gender-divergent Oatp expression in liver is caused by male-pattern GH secretion pattern and androgens. In kidney, gender-divergent Oatp expression is exclusively caused by stimulation by androgens.

Androgens↗

Biochemical characterization, molecular cloning and expression of laccases - a divergent gene family - in poplar.

The nature of the enzyme(s) involved in the dehydrogenative polymerization of lignin monomers is still a matter of debate. Potential candidates include laccases which have recently received attention due to their capacity to oxidize lignin monomers and close spatial and temporal correlation with lignin deposition. We have characterized two H2O2-independent phenoloxidases with approximate molecular masses of 90 kDa and 110 kDa from cell walls of Populus euramericana xylem that are capable of oxidizing coniferyl alcohol. The 90-kDa protein was purified to apparent homogeneity and extensively characterized at the biochemical and structural levels. To our knowledge, this is the first report of a plant laccase purified to homogeneity from a lignifying tissue of an angiosperm. The cDNA clones corresponding to the 90-kDa and 110-kDa proteins, lac90 and lac110, were obtained by a PCR-based approach using specific oligonucleotides derived from peptide sequences. Sequence analysis indicated that lac90 and lac110 encoded two distinct laccases. In addition, heterologous screening using an Acer pseudoplatanus laccase cDNA enabled us to obtain three additional cDNAs (lac1, lac2, lac3) that did not correspond to lac90 and lac110. The five laccase cDNAs correspond to a highly divergent multigene family but Northern analysis with gene-specific probes indicated that all of the genes are exclusively and abundantly expressed in stems. These results highlight the polymorphism of plant laccases by an integrated biochemical and molecular approach, and provide the tools that will enable us to clearly determine the function of these enzymes in plants by molecular and genetic approaches.

Acrolein↗

The 14-3-3 proteins in the teleost fish rainbow trout (Oncorhynchus mykiss).

We report studies of 14-3-3 genes in rainbow trout, adding to current understanding of the molecular evolution of this multigene family and its functional importance in fish. Ten genes were identified that are apparent duplicates of five ancestors. The duplicated 14-3-3 genes diverged rapidly and their cladogram is markedly different from the phylogenetic tree. The mean rate of nonsynonymous divergence of trout 14-3-3 genes is one order of magnitude greater than that of mammalian genes. An evolutionarily recent genome duplication in salmonid fish relaxed functional constraints, and selection favored establishment of novel isoforms. Differences in tissue distribution of 14-3-3 genes were minor; however, results of 31 microarray experiments showed divergence of expression profiles, which was related to structural divergence of the duplicates. We observed remarkable coordination of expression of all isoforms in our study of stress response in the brain. Profiles of the 14-3-3 genes correlated with a large group of chaperones and genes involved in cell communication and signal transduction. We studied embryonic expression of 14-3-3 genes and found abundant transcripts in the rapidly growing and differentiating parts of embryos such as eyes, tail bud and yolk syncytium during somitogenesis and in gills and pectoral fins after completion of somitogenesis. Consistent expression was observed in the neural crest, which is known to have high morphogenetic potential.

14-3-3 Proteins↗

Ontogeny of vascular growth factors in perinatal sheep myocardium.

OBJECTIVE: To examine developmental changes in myocardial gene expression of previously identified regulators of vascular growth. METHODS: Ovine left (LV) and right ventricle (RV) samples were obtained at four time points: 95 days' and 140 days' gestation (term = 145 days) and 7 days and 8 weeks postnatally. mRNA and protein levels of vascular endothelial growth factor (VEGF), its respective receptors (Flk-1 and Flt-1), basic fibroblast growth factor (bFGF), transforming growth factor-beta1 (TGF-beta1), and endothelial nitric oxide synthase (eNOS) were measured at these different time points. RESULTS: RV but not LV VEGF mRNA levels decreased postnatally, although VEGF protein expression remained unchanged after birth. Flt-1 mRNA expression was divergent between ventricles, although the protein expression pattern was similar in RV and LV, decreasing with maturation. RV and LV Flk-1 mRNA decreased between 95 days and 140 days, remaining stable thereafter, while protein levels only decreased after birth. bFGF protein levels were highest in the LV at 140 days, and decreased after birth but remained unchanged in the RV throughout the period examined. TGF-beta1 and eNOS levels were highest early in gestation, decreasing with maturation in both ventricles. CONCLUSION: Developmentally regulated ventricle-specific expression of VEGF, Flt-1, Flk-1, TGF-beta1, bFGF, and eNOS was demonstrated in the ovine myocardium. These findings suggest these proteins may participate in coronary vascular remodeling during the perinatal period and underscore the importance of studying the relationships among transcription factors, target genes, and anatomic/physiologic changes in the whole animal.

Aging↗

Exploring the clinical and biological significance of the cell cycle-related gene CHMP4C in prostate cancer.

BACKGROUND: Prostate cancer (PCa) stands as the second most prevalent malignancy impacting male health, and the disease's evolutionary course presents formidable challenges in the context of patient treatment and prognostic management. Charged multivesicular body protein 4 C (CHMP4C) participates in the development of several cancers by regulating cell cycle functions. However, the role of CHMP4C in prostate cancer remains unclear. METHODS: In terms of bioinformatics, multiple PCa datasets were employed to scrutinize the expression of CHMP4C. Survival analysis coupled with a nomogram approach was employed to probe into the prognostic significance of CHMP4C. Gene set enrichment analysis (GSEA) was conducted to interrogate the functional implications of CHMP4C. In terms of cellular experimentation, the verification of RNA and protein expression levels was executed through the utilization of qRT-PCR and Western blotting. Upon the establishment of a cell line featuring stable CHMP4C knockdown, a battery of assays, including Cell Counting Kit-8 (CCK-8), wound healing, Transwell, and flow cytometry, were employed to discern the impact of CHMP4C on the proliferation, migration, invasion, and cell cycle function of PCa cells. RESULTS: The expression of CHMP4C exhibited upregulation in both PCa cells and tissues, and patients demonstrating elevated CHMP4C expression levels experienced a notably inferior prognosis. The nomogram, constructed using CHMP4C along with clinicopathological features, demonstrated a commendable capacity for prognostic prediction. CHMP4C knockdown significantly inhibited the proliferation, migration, and invasion of PCa cells (LNcaP and PC3). CHMP4C could impact the advancement of the PCa cell cycle, and its expression might be regulated by berberine. Divergent CHMP4C expression among PCa patients could induce alterations in immune cell infiltration and gene mutation frequency. CONCLUSIONS: Our findings suggest that CHMP4C might be a prognostic biomarker in PCa, potentially offering novel perspectives for the advancement of precision therapy for PCa.

Humans↗

Multiple regions of a divergent promoter control the expression of the Agrobacterium rhizogenes aux1 and aux2 plant oncogenes.

The two auxin biosynthesis genes, aux1 and aux2 of Agrobacterium rhizogenes strain A4, are located on opposite DNA strands with a short integenic region (394 bp) between their coding sequences. A functional analysis of this divergent promoter is presented. The transcription initiation sites of the two aux genes were determined and regions important for promoter activity were identified by deletion and transient expression analyses in tobacco protoplasts. The promoter activity of the aux intergenic region was demonstrated. A strong enhancer element contained within an 84 bp promoter fragment was identified. Far upstream regions were shown to have negative effects on the promoter activity of the short intergenic region. Interactions between positive elements in the intergenic region and negative effects of the upstream sequences may be the basis of strict control of the auxin biosynthesis necessary for the induction and maintenance of hairy root growth.

Base Sequence↗

Language, cognition, and short-term memory in individuals with Down syndrome.

The developmentally emerging phenotype of language and cognition in individuals with Down syndrome is summarized on the basis of the project's prior work. Identified are a) the emerging divergence of expressive and receptive language, b) the emerging divergence of lexical and syntactic knowledge in each process, and c) the emerging divergence within cognitive skills of auditory short-term memory and visuospatial short-term memory from other visuospatial skills. Expressive syntax and auditory short-term memory are identified as areas of particular difficulty. Evidence for the continued acquisition of language skills in adolescence is presented. The role of the two components of working memory, auditory and visual, in language development is investigated in studies of narrative and longitudinal change in language skills. Predictors of individual differences during six years of language development are evaluated through hierarchical linear modelling. Chronological age, visuospatial short-term memory, and auditory-short term memory are identified as key predictors of performance at study entry, but not individual change over time, for expressive syntax. The same predictors account for variation in comprehension skill at study outset; and change over the six years can be predicted by chronological age and the change in visuospatial short-term memory skills.

Cognition Disorders↗

Stable expression of HB24, a diverged human homeobox gene, in T lymphocytes induces genes involved in T cell activation and growth.

A diverged homeobox gene, HB24, which is known to be induced following lymphocyte activation, was introduced into Jurkat T cells under the control of a constitutive promoter. Stable transfectants of HB24 were established that expressed high levels of HB24 mRNA and possessed an altered phenotype suggestive of activated T cells. A number of genes known to be induced following T cell activation and associated with cell growth were increased in the transfectants, including c-fos, c-myc, c-myb, HLA-DR, lck, NF-kappa B, interleukin-2 and interleukin-2 receptor alpha (IL-2R alpha). Analysis of IL-2R alpha expression by transient transfection of IL-2R alpha promoter constructs into the HB24 transfectants revealed constitutive expression (about 60% of phytohemagglutinin- and phorbol ester-activated Jurkat cells) that was dependent on the kappa B site in the IL-2R alpha promoter. Furthermore, as a consequence of the increased HB24 mRNA levels, the Jurkat HB24 transfectants proliferated more rapidly than control cell lines. Thus, stable expression of HB24 confers an activation phenotype on a human T cell line, implicating this gene as an important transcriptional factor during T cell activation and growth.

Base Sequence↗

Divergently transcribed overlapping genes expressed in liver and kidney and located in the 11p15.5 imprinted domain.

Human chromosomal band 11p15.5 has been shown to contain genes involved in the development of several pediatric and adult tumors and in Beckwith-Wiedemann syndrome (BWS). Overlapping P1 artificial chromosome clones from this region have been used as templates for genomic sequencing in an effort to identify candidate genes for these disorders. PowerBLAST identified several matches with expressed sequence tags (ESTs) from fetal brain and liver cDNA libraries. Northern blot analysis indicated that two of the genes identified by these ESTs encode transcripts of 1-1.5 kb with predominant expression in fetal and adult liver and kidney. With RT-PCR and RACE, full-length transcripts were isolated for these two genes, with the largest open reading frames encoding putative proteins of 253 and 424 amino acids. Database comparison of the predicted amino acid sequence of the larger transcript indicated homology to integral membrane organic cation transporters; hence, we designate this gene ORCTL2 (organic cation transporter-like 2). An expressed sequence polymorphism provided evidence that the ORCTL2 gene exhibits "leaky" imprinting in both human fetal kidney and human fetal liver. The mouse orthologue (Orctl2) was identified, and a similar polymorphism was used to demonstrate maternal-specific expression of this gene in fetal liver from interspecific F1 mice. The predicted protein of the smaller gene showed no significant similarity in the database. Northern and RACE analyses suggest that this gene may have multiple transcription start sites. Determination of the genomic structure in humans indicated that the 5'-end of this transcript overlaps in divergent orientation with the first two exons of ORCTL2, suggesting a possible role for antisense regulation of one gene by the other. We, therefore, provisionally name this second transcript ORCTL2S (ORCTL2-antisense). The expression patterns of these genes and the imprinted expression of ORCTL2 are suggestive of a possible role in the development of Wilms tumor (WT) and hepatoblastoma. Although SSCP analysis of 62 WT samples and 10 BWS patients did not result in the identification of any mutations in ORCTL2 or ORCTL2S, it will be important to examine their expression pattern in tumors and BWS patients, since epigenetic alteration at these loci may play a role in the etiology of these diseases.

Amino Acid Sequence↗

Gene expression differences in mice divergently selected for methamphetamine sensitivity.

In an effort to identify genes that may be important for drug-abuse liability, we mapped behavioral quantitative trait loci (bQTL) for sensitivity to the locomotor stimulant effect of methamphetamine (MA) using two mouse lines that were selectively bred for high MA-induced activity (HMACT) or low MA-induced activity (LMACT). We then examined gene expression differences between these lines in the nucleus accumbens, using 20 U74Av2 Affymetrix microarrays and quantitative polymerase chain reaction (qPCR). Expression differences were detected for several genes, including Casein Kinase 1 Epsilon (Csnkle), glutamate receptor, ionotropic, AMPA1 (GluR1), GABA B1 receptor (Gabbr1), and dopamine- and cAMP-regulated phosphoprotein of 32 kDa (Darpp-32). We used the www.WebQTL.org database to identify QTL that regulate the expression of the genes identified by the microarrays (expression QTL; eQTL). This approach identified an eQTL for Csnkle on Chromosome 15 (LOD = 3.8) that comapped with a bQTL for the MA stimulation phenotype (LOD = 4.5), suggesting that a single allele may cause both traits. The chromosomal region containing this QTL has previously been associated with sensitivity to the stimulant effects of cocaine. These results suggest that selection was associated with (and likely caused) altered gene expression that is partially attributable to different frequencies of gene expression polymorphisms. Combining classical genetics with analysis of whole-genome gene expression and bioinformatic resources provides a powerful method for provisionally identifying genes that influence complex traits. The identified genes provide excellent candidates for future hypothesis-driven studies, translational genetic studies, and pharmacological interventions.

Animals↗

In situ hybridization with 33P-labeled RNA probes for determination of cellular expression patterns of liver transcription factors in mouse embryos.

Murine hepatocyte nuclear factor-3beta (HNF-3beta) protein is a member of a large family of developmentally regulated transcription factors that share homology in the winged helix/fork head DNA binding domain and that participate in embryonic pattern formation. HNF-3beta also mediates cell-specific transcription of genes important for the function of hepatocytes, intestinal and bronchiolar epithelium, and pancreatic acinar cells. We have previously identified a hepatocyte and pancreatic cut-homeodomain transcription factor, HNF-6, which is required for HNF-3beta promoter activity. In this study, we used in situ hybridization studies of stage-specific embryos to demonstrate that HNF-6 and its target gene, HNF-3beta, are coexpressed in the foregut endoderm and in the pancreatic and hepatic diverticulum. More detailed analysis of HNF-6 and HNF-3beta's developmental expression patterns provides evidence of colocalization in hepatocytes, intestinal epithelium, and pancreatic ductal epithelium and exocrine acinar cells. In support of the role of HNF-6 in regulating HNF-3beta expression in developing hepatocytes, their liver expression levels are both transiently reduced between 14 and 15 days of gestation. At day 18 of gestation and in adult pancreas, HNF-6 and HNF-3beta transcripts remain colocalized in the exocrine acinar cells, but their expression patterns diverge in endocrine cells. HNF-3beta expression is restricted to the endocrine cells of the islets of Langerhans, whereas the ductal epithelium expresses HNF-6. We discuss these expression patterns with respect to specification of hepatocytes and differentiation of the endocrine and exocrine pancreas.

Animals↗