Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Organogenesis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed2005

Stem cells, tissue engineering and organogenesis in transplantation.

Tissue engineering is an attempt to generate living tissues for surgical transplantation. In vitro and in vivo approaches have led to the production of vascular and cardiovascular components, bones, cartilages and gastrointestinal tissues. Organogenesis has a different aim, which is to create transplantable organs from embryonic tissue implanted into the recipient's omentum. This approach has been successful in creating kidneys and pancreases in animals. The use of stem cells in organogenesis and in tissue engineering has vastly enlarged the potential for clinical applications. The technique of nuclear transfer offers the possibility of creating cells, which are genetically identical to the host. Tissue engineering and organogenesis represent the future of transplantation in medicine. The progress in this field is of tremendous importance because it can produce a new generation of morphologically complex tissues and organs. In this review, the most relevant experiences in this area are summarized, including its perspectives for therapeutical applications.

Animals↗
PubMed2006

CNBP regulates forebrain formation at organogenesis stage in chick embryos.

We recently demonstrated that Cellular Nucleic acid Binding Protein (CNBP)(-/-) mouse embryos exhibit forebrain truncation due to a lack of proper morphogenetic movements of the anterior visceral endoderm (AVE) during pre-gastrulation stage (Chen, W., Liang, Y., Deng, W., Shimizu, K., Ashique, A.M., Li, E., Li, Y.P., 2003. The zinc-finger protein CNBP is required for forebrain formation in the mouse, Development 130, 1367-1379). However, CNBP expression pattern in the mouse forebrain suggests that CNBP may have more direct effects during forebrain development. Our data show that CNBP is expressed in tissues of early chick embryo that are the equivalent to the mouse embryo. Using a combination of RNAi-silencing and Retrovirus-misexpression approaches, we investigated the temporal function of CNBP in the specification/development of the chick forebrain during organogenesis. The silencing of CNBP expression resulted in forebrain truncation and the absence of BF-1, Six3 and Hesx1 expression, but not Otx2 in chick embryos. Misexpression of CNBP induced the expression of BF-1, Six3 and Hesx1 in the hindbrain, but not the expression of Otx2. These results offer novel insights into the function of CNBP during organogenesis as the regulator of forebrain formation and a number of rostral head transcription factors. Moreover, CNBP and Otx2 may play roles as regulators of forebrain formation in two parallel pathways. These new insights into CNBP functions underscore the essential role of CNBP in forebrain formation during chick embryo organogenesis.

Animals↗
PubMed2002

DNA repair during organogenesis.

DNA damage caused by genotoxic agents can impact on virtually any cellular process due to its ability to affect gene expression and subsequent gene products. The importance of repairing damaged DNA is evidenced by the variety of DNA repair pathways that have evolved in all living organisms, and the human syndromes caused by a lack of this repair ability. This review focuses on the expression and activity of DNA repair pathways during mammalian organogenesis, and the role of these pathways in ensuring the stability of the conceptal genome. DNA repair capacity may play a role also in the response of the conceptus to genotoxic agents that may induce malformations; the consequences of exposure to a genotoxic agent during organogenesis depend on the extent of the damage and on the ability of the embryo to respond by repairing DNA or arresting cell division. The four main repair pathways (nucleotide excision repair, base excision repair, mismatch repair, and recombination repair) are expressed to various degrees during organogenesis, as are members of the genotoxic stress-activated cell cycle checkpoint pathways. Developmental-stage-specific alterations in transcript levels, protein levels, as well as activity, indicate that the regulation of DNA repair pathways during development is complex. The importance of DNA repair pathways in endogenous damage control is illustrated by the sensitivity of development to their disruption if some of these genes are mutated. Furthermore, the conceptus has a limited capacity to alter DNA repair responses following exposure to genotoxic agents.

Animals↗
PubMedDate not supplied

Embryotoxic effects of Solanum lycocarpum St. Hill fruits consumption during preimplantation and organogenesis in rats.

Solanum lycocarpum St. Hill is a common plant in the Brazilian savanna. This plant has an alkaloid with stereospecific configuration to the synthesis of steroid hormones. Since the plant may be consumed by pregnant animals, the present study was undertaken to determine the possible embryotoxic effects of S. lycocarpum fruit ingestion (3% added to the diet) during preimplantation (from the first to the sixth days of gestation) or during organogenesis in rats (from the sixth to the sixteenth days of gestation). Few differences were observed in food and water consumption without biological importance. The placental weight in the group that received the plant during the organogenesis period was decreased. An increase in sternebra abnormalities was observed in animals treated with the plant during organogenesis. Olfactory bulb hemorrhage was increased in the group that received the plant during preimplantation when compared to the control group. These results indicate that consumption of S. lycocarpum at 3% in diet during pregnancy cause slight toxicological effects. Other studies have to be conducted to better investigate the causes of toxicity and other toxic effects of higher levels of exposure to this plant.

Analysis of Variance↗
PubMed2006

Sustained Notch signaling in progenitors is required for sequential emergence of distinct cell lineages during organogenesis.

Mammalian organogenesis results from the concerted actions of signaling pathways in progenitor cells that induce a hierarchy of regulated transcription factors critical for organ and cell type determination. Here we demonstrate that sustained Notch activity is required for the temporal maintenance of specific cohorts of proliferating progenitors, which underlies the ability to specify late-arising cell lineages during pituitary organogenesis. Conditional deletion of Rbp-J, which encodes the major mediator of the Notch pathway, leads to premature differentiation of progenitor cells, a phenotype recapitulated by loss of the basic helix-loop-helix (bHLH) factor Hes1, as well as a conversion of the late (Pit1) lineage into the early (corticotrope) lineage. Notch signaling is required for maintaining expression of the tissue-specific paired-like homeodomain transcription factor, Prop1, which is required for generation of the Pit1 lineage. Attenuation of Notch signaling is necessary for terminal differentiation in post-mitotic Pit1+ cells, and the Notch-repressed Pit1 target gene, Math3, is specifically required for maturation and proliferation of the GH-producing somatotrope. Thus, sustained Notch signaling in progenitor cells is required to prevent conversion of the late-arising cell lineages to early-born cell lineages, permitting specification of diverse cell types, a strategy likely to be widely used in mammalian organogenesis.

Animals↗
PubMed2005

Lymphoid organogenesis in the intestine.

Lymphoid organogenesis is dependent upon a series of intricate cellular interactions involving adhesion molecules, chemokines, and cytokines that generate fully compartmentalized lymphoid structures. Development of organized lymphoid structures in the intestine begins prenatally and continues through adulthood, with constant adaptations to changes in the luminal flora. While much is known about the mechanisms that govern the development of macroscopic intestinal lymphoid structures (mesenteric lymph node and Peyer's patches), the organogenesis of the microscopic lymphoid tissues (including cryptopatches and isolated lymphoid follicles) is an emerging field. This review examines the current state of knowledge about organogenesis of the known types of organized lymphoid tissue in the intestine and identifies unique and common features in the development of each of the structures discussed.

Animals↗
PubMed2006

Gut-like structures from mouse embryonic stem cells as an in vitro model for gut organogenesis preserving developmental potential after transplantation.

Recently, we reported the formation of gut-like structures from mouse ESCs in vitro. To determine whether ESCs provide an in vitro model of gastrointestinal (GI) tracts and their organogenesis, we investigated the morphological features, formation process, cellular development, and regional location within the GI tract by immunohistochemistry, electron microscopy, and reverse transcription-polymerase chain reaction. We also examined the developmental potential by transplantation into kidney capsules. The results demonstrated that Id2-expressing epithelium developed first, alpha-smooth muscle actin appeared around the periphery, and finally, the gut-like structures were formed into a three-layer organ with well-differentiated epithelium. A connective tissue layer and musculature with interstitial cells of Cajal developed, similar to organogenesis of the embryonic gut. Enteric neurons appeared underdeveloped, and blood vessels were absent. Many structures expressed intestinal markers Cdx2 and 5-hydroxytryptamine but not the stomach marker H(+)/K(+) ATPase. Transplants obtained blood vessels and extrinsic nerve growth from the host to prolong life, and even grafts of premature structures did not form teratoma. In conclusion, gut-like structures were provided with prototypical tissue components of the GI tract and are inherent in the intestine rather than the stomach. The formation process was basically same as in gut organogenesis. They maintain their developmental potential after transplantation. Therefore, gut-like structures provide a unique and useful in vitro system for development and stem cell studies of the GI tract, including transplantation experiments.

Animals↗
PubMed2002

Modulation of nitric oxide concentration and lipid metabolism by 15-deoxy Delta12,14prostaglandin J2 in embryos from control and diabetic rats during early organogenesis.

The concentration of 15-deoxy Delta(12,14)PGJ(2) (15dPGJ(2)) and its effects on nitric oxide generation and neutral lipid in embryos from control and neonatal streptozotocin-induced (n-stz) diabetic rats during organogenesis were investigated. 15dPGJ(2) is produced in embryos during organogenesis, and its production is lower in embryos of n-stz diabetic rats than in embryos from control rats. Nitrate and nitrite concentrations were higher in embryos from n-stz diabetic rats and were reduced in the presence of 15dPGJ(2) both in embryos from control and diabetic rats. Thus, decreased 15dPGJ(2) concentrations in embryos from n-stz diabetic rats may be related to the high nitric oxide concentrations found in those embryos. Exogenous 15dPGJ(2) decreased cholesterol and cholesteryl ester concentrations in embryos from control and n-stz diabetic rats, and reduced triacylglycerol concentrations in control embryos. Incorporation of [(14)C]acetate into lipids showed decreased de novo synthesis of cholesteryl ester and triacylglycerides in embryos from n-stz diabetic rats compared with controls. Exogenous 15dPGJ(2) reduced the incorporation of [(14)C]acetate into triacylglycerides, cholesterol and cholesteryl ester in embryos from both control and n-stz diabetic rats. 15dPGJ(2) is present in embryos during organogenesis, and reduces embryonic nitric oxide production and lipid synthesis. The lower 15dPGJ(2) concentration in embryos from n-stz diabetic rats may result in developmental alterations in this diabetic model.

Acetates↗
PubMed2001

Induction of ureter branching as a response to Wnt-2b signaling during early kidney organogenesis.

Epithelial-mesenchymal tissue interactions play a central role in vertebrate organogenesis, but the molecular mediators and mechanisms of these morphogenetic interactions are still not well characterized. We report here on the expression pattern of Wnt-2b during mouse organogenesis and on tests of its function in epithelial- mesenchymal interactions during kidney development. Wnt-2b is expressed in numerous developing organs in the mouse embryo, including the kidney, lung, salivary gland, gut, pancreas, adrenal gland, and genital tubercle. Additional sites of expression include the branchial arches and craniofacial placodes such as the eye and ear. The data suggest that the expression of Wnt-2b is associated with organs regulated by epithelial-mesenchymal interactions. It is typically localized in the capsular epithelium or peripheral mesenchymal cells of organ rudiments, e.g., the perinephric mesenchymal cells in the region of the presumptive renal stroma in the developing kidney at E11.5. Functional studies of the kidney demonstrate that cells expressing Wnt-2b are not capable of inducing tubule formation but instead stimulate ureter development. Incubation of isolated ureteric buds on such cells supports bud growth and branching. In addition, recombination of Wnt-2b-pretreated ureteric bud tissue with isolated nephrogenic mesenchyme results in a recovery of organogenesis and the expression of epithelial genes within the reconstituted organ explant. Lithium, a known activator of Wnt signaling (Hedgepeth et al. [1997] Dev Biol 185:82-91), is also sufficient to promote ureter branching in the reconstituted kidney in a comparable manner to Wnt-2b signaling, whereas Wnt-4, which induces tubules, neither supports the growth of a ureteric bud nor leads to reconstitution of the ureteric bud with the kidney mesenchyme. We conclude that Wnt-2b may act in the mouse kidney as an early mesenchymal signal controlling morphogenesis of epithelial tissue, and that the Wnt pathway may regulate ureter branching directly. In addition, Wnt signals in the kidney differ qualitatively and are specific to either the epithelial ureteric bud or the kidney mesenchyme.

3T3 Cells↗
PubMedDate not supplied

Neoplastic potential of germ cells in relation to disturbances of gonadal organogenesis and changes in karyotype.

The study consisted of 46 intersexual patients who underwent gonadectomy at the age of 3 months to 19 years because of gonadal dysgenesis (GD; 40 cases) or true hermaphroditism (bisexual gonads; 6 cases). In patients with GD, the incidence of the 46,XY karyotype was 67.5%, whereas the remaining patients exhibited numerical and structural aberrations of sex chromosomes (NSASs), and all patients with bisexual gonads revealed NSAS. Seminoma was diagnosed in 1 patient with the 46,XY karyotype and pure GD (streak gonads). Intratubular carcinoma in situ (CIS) appeared as an exclusive lesion in 61.5% of 13 patients with mixed GD, in 54% of 11 patients with partial GD (bilateral testes), in 16.7% of 6 patients with bisexual gonads, and in none of 13 patients with pure GD. CIS also appeared in tubules in the vicinity of sex cord-derived tumors (gonadoblastoma nests and unclassified mixed germ cell-sex cord-stromal tumor; MGCSCST) and within the tumors. In 3 patients, gonadoblastoma replaced the whole bilateral gonads and is referred to as gonadoblastoma-only GD. The incidence of neoplastic lesions (mostly bilateral) was 90.9% in patients with partial GD, 76.9% (mostly unilateral) in patients with mixed GD, 23.1% (unilateral) in patients with pure GD, and 16.7% (unilateral) in patients with bisexual gonads. Disregarding types of disturbances of gonadal organogenesis, the incidence of lesions was 71.4% in 28 patients with the 46,XY karyotype and 35.3% in 17 patients with NSAS. We conclude, first, that NSAS is not a prerequisite for the appearance of GD and GD is more frequently associated with the 46,XY karyotype. Second, the spectrum of germ cell neoplastic lesions in GD is wider than reported. Besides germ cell carcinoma, CIS, and gonadoblastoma nests, the spectrum also includes a tumor of gonadoblastoma-only in cases of GD and MGCSCST. Third, the incidence of neoplastic lesions is related more to the severity of the disturbances of gonadal organogenesis than it is to aberrations in sex chromosomes. Fourth, less disturbed testicular organogenesis predisposes these patients more toward germ cell neoplastic lesions, which suggests that the testicular environment of a dysgenetic gonad plays an important role in germ cell neoplasia initiation, maintenance, or both.

Adolescent↗
PubMed1990

Experimental yolk sac dysfunction as a model for studying nutritional disturbances in the embryo during early organogenesis.

Our investigations concerning the importance of cell surface macromolecules during embryonic development led us to the discovery in 1961 that heterologous anti-rat kidney serum produced teratogenesis, growth retardation and embryonic death when injected into the pregnant rat during early organogenesis. It was established that IgG was the teratogenic agent, primarily directed against the visceral yolk sac (VYS) but not the embryo. Heterologous anti-rat VYS serum was prepared which was teratogenic localized in the VYS and served as a model for producing VYS dysfunction and embryonic malnutrition. The role of the yolk sac placenta in histiotrophic nutrition is now recognized to be critical for normal embryonic development during early organogenesis in the rodent. VYS antiserum affects embryonic development primarily by inhibiting endocytosis of proteins by the VYS endoderm, resulting in a reduction in the amino acids supplied to the embryo. Our laboratory has recently developed teratogenic monoclonal yolk sac antibodies (MCA) which can be utilized; to study VYS plasma membrane synthesis and recycling, to compare yolk sac function among different species, and to identify components of the plasma membrane involved in pinocytosis. MCA prepared against certain VYS antigens provide an opportunity to study embryonic nutrition with minimal interference with the nutritional state of the mother. Recent developments in the study of the human yolk sac along with our laboratory's ability to isolate a spectrum of yolk sac antigens, prepare monoclonal antibodies, and perform functional studies, should provide information that will increase our understanding of yolk sac function and dysfunction in the human and determine the relative importance of various amino acids to normal development during mammalian organogenesis.

Animals↗
PubMed1993

Unique expression pattern of the FGF receptor 3 gene during mouse organogenesis.

The actions of fibroblast growth factors (FGFs) are mediated via a family of four closely related FGF receptor genes (FGFRs 1-4). FGFR1, FGFR2, and FGFR4 have unique patterns of expression during embryogenesis suggesting that these receptors mediate different functions of FGFs during development. In the present study, we used in situ hybridization analysis to show that FGFR3 also has a unique pattern of expression during organogenesis. Like FGFR1 and FGFR2, FGFR3 was expressed in the germinal epithelium of the neural tube (9.5-16.5 days pc). However, at 1 day postpartum and in the adult brain, FGFR3 was expressed diffusely and localized in cells with morphologic characteristics of glia, a pattern distinctly different from the discrete neuronal expression of FGFR1. FGFR3 was also expressed at high levels in differentiating hair cells of the cochlear duct, but was not detected in other sensory epithelia. Outside the nervous system, the highest level of FGFR3 expression was found in the cartilage rudiments of developing bone. During endochondral ossification, FGFR3 was expressed exclusively in resting cartilage, a pattern distinct from FGFR1 and FGFR2 which are also expressed during this process. Unlike FGFR1 and FGFR2, FGFR3 was not detected in most other epithelial or mesenchymal tissues during these stages of organogenesis. The unique expression pattern of FGFR3 compared with the other FGF receptors strongly suggests that FGFR3 performs specific functions during organogenesis.

Animals↗
PubMed1995

Effects of cocaine administration during early organogenesis on prenatal development and postnatal growth in mice.

Cocaine use has been associated with adverse developmental effects in humans. However, clinical reports both confirm and deny an association between cocaine use and malformations. Similarly, differences in species and strain, as well as route and timing of cocaine administration, have added to the difficulties in determining the teratogenicity of cocaine in animal models. This study was undertaken to compare the effects of dose, route, and timing of cocaine administration in ICR mice during early organogenesis. A single intraperitoneal (ip) administration of cocaine ( > or = 60 mg/kg) on Day 9 of gestation (plug day = 1) produced maternal lethality. The predominant developmental effect of cocaine administration was an increase in the percentage of litters exhibiting an enlarged renal pelvis. Despite a high incidence of affected pups at these doses, the enlargement was not severe. These results, in agreement with previous reports, provide further evidence that the developing urogenital system is sensitive to cocaine administration. When cocaine was administered using a subcutaneous route, pup weights were greater and the incidence of enlarged renal pelvis was lower than when an ip route was used. To better mimic human binge cocaine abuse, the toxicity of a "split dose" was determined. A 60 mg/kg dose was administered using one administration of 60 mg/kg, two treatments of 30 mg/kg, or three administrations of 20 mg/kg with 1 hr separating the treatments. The incidence of enlarged renal pelvis was similar when cocaine was administered as one or two but was decreased when cocaine was administered as three treatments. Both the route and split-dose studies suggest that high-peak serum concentrations are required to perturb development. There were no differences in the incidence or severity of enlarged renal pelvis when cocaine was administered on Day 8, 9, or 10 or on all 3 days of gestation. This suggested that the increase in enlarged renal pelvis may not be a specific teratogenic effect of cocaine administration but may be a delay of normal development induced by cocaine exposure during this early period of organogenesis. To address this hypothesis, cocaine was administered on Day 9 using an ip route and the pups were allowed to be naturally born. In pups whose mothers received cocaine there was an increase in postnatal deaths and a trend toward a reduction in pup body weight/litter at Postnatal Day 21. However, when renal morphology was assessed on Postnatal Day 21 no abnormal kidneys were seen. This supports the hypothesis that enlarged renal pelvis produced by cocaine administration during early organogenesis represents a developmental delay and not a persistent teratogenic defect. These studies suggest that high peak cocaine concentrations are required to delay normal kidney morphogenesis in mice.

Animals↗
PubMed1987

Effect of polyamine biosynthetic inhibitors on alkaloids and organogenesis in tobacco callus cultures.

We studied the effects of inhibitors of ornithine decarboxylase (ODC), arginine decarboxylase (ADC) and spermidine synthase (Spd synthase) on organogenesis and the titers of polyamines (PA) and alkaloids in tobacco calli. DL-alpha-diffluromethylarginine (DFMA) and D-arginine (D-Arg), both inhibitors of ADC activity, were more effective than DL-alpha-difluromethylorinithine (DFMO), an inhibitor of ODC, in reducing titers of PA and the putrescine (Put)-derived alkaloids (nornicotine and nicotine). Dicyclohexylammonium sulfate (DCHA), an inhibitor of Spd synthase, was also more efficient than DFMO in reducing PA and alkaloid levels. Root organogenesis is inversely related to the titers of Put and alkaloids. Thus, DFMA and D-Arg, which strongly inhibit Put and alkaloid biosynthesis, markedly promote root organogenesis, while control callus with high Put and alkaloid content showed poor root organization. These results suggest that morphological differentiation is not required for activation of secondary metabolic pathways and support the view that ADC has a major role in the generation of Put going to the pyrrolidine ring of tobacco alkaloids.

Arginine↗
PubMed2006

Distinct reorganization of the genome transcription associates with organogenesis of somatic embryo, shoots, and roots in rice.

Most plant cells retain the capacity to differentiate into all the other cell and organ types that constitute a plant. However, genome-wide transcriptional activities underlying the process of cell differentiation are poorly understood, especially in monocot plants. Here we used a rice (Oryza sativa) cell culture system to generate somatic embryos, which were further induced into shoots and roots. The global transcriptional reorganization during the development of somatic embryos, shoots, and roots from cultured cells was studied using a rice whole genome microarray and verified by RNA blotting analysis of representative genes. Overall, only 1-3% of expressed genes were differentially regulated during each organogenesis process at the examined time point. Also metabolic pathways were minimally regulated. Thus the genes that dictating organ formation should be relatively small in number. Comparison of these three transcriptomes revealed little overlap during these three organogenesis processes. These results indicate that each organogenesis involves specific reorganization of genome expression.

Cells, Cultured↗
PubMed2001

Genotypic control of high-frequency adventitious shoot regeneration via somatic organogenesis in loblolly pine.

Mature zygotic embryos of 24 genotypes of loblolly pine (Pinus taeda L.) were used as explants to establish an adventitious shoot regeneration system through somatic organogenesis. Callus formation frequencies of 18.2 (genotype 11-1103) -77.7% (genotype 7-100) have been induced from mature zygotic embryos of all genotypes tested on callus induction medium (basal salts) containing 2,4-dichlorophenoxyacetic acid (2,4-D) or alpha-naphthaleneacetic acid (NAA), 6-benzyladenine (BA), and kinetin. Adventitious shoot regeneration via organogenesis with the frequency of 5.4 (genotype 11-1103 and 7-2) -77.2% (genotype 8-1082) was obtained from callus and tissue cultures derived from mature zygotic embryos of 24 genotypes of loblolly pine. The highest mean number of 18 adventitious buds per piece of callus 0.5x0.5 cm(2) in size was obtained from genotype 8-1082. Elongation of adventitious buds was achieved on TE medium supplemented with 0.5 mg/l indole-3-butyric acid (IBA) and 1 mg/l BA. After rooting, regenerated plantlets were established in soil. These results suggested that adventitious shoot regeneration via somatic organogenesis was influenced by the genotypes. The in vitro regeneration procedure established in this investigation could be used for clonal micropropagation of some genotypes of loblolly pine, as well as for establishing a transformation system in coniferous species.

Journal Article↗
PubMed2000

In vitro control of organogenesis and body patterning by activin during early amphibian development.

In the process of amphibian development, an embryonic body plan is established through cell division, sequential gene expression, morphogenesis and cell differentiation. The mechanism of body patterning is complex and includes multiple induction events. Activin, a TGF-beta family protein, can induce several kinds of mesodermal and endodermal tissues in animal cap explants in a dose-dependent manner. In a recent study of the role of activin in organogenesis, we succeeded in raising a beating heart by treating animal caps with a high concentration of activin. Activin also participates in kidney organogenesis in combination with retinoic acid. An embryonic kidney induced by activin and retinoic acid in vitro can function in vivo when it is transplanted into a larva in which pronephros rudiments have already been removed. Further, the activin-treated animal caps clearly show organizer actions that are closely related to body patterning along the anteroposterior axis. These experiments will help to serve as a model system for understanding organogenesis and body patterning at the cellular and molecular levels.

Activins↗
PubMed2002

Abnormal organogenesis of Peyer's patches in mice deficient for NF-kappaB1, NF-kappaB2, and Bcl-3.

BACKGROUND & AIMS: Nuclear factor (NF) kappaB1, NF-kappaB2, and Bcl-3 encode for proteins of the NF-kappaB/Rel/IkappaB families, known as regulators of innate and adoptive immune responses. Targeted disruption of these genes showed essential roles in lymphoid organ development and organization. METHODS: NF-kappaB1-, NF-kappaB2-, and Bcl-3-deficient mouse lines were established, and their role in organogenesis of Peyer's patches (PP) was investigated. RESULTS: Macroscopic inspection showed a reduced number and size of PP in Bcl-3(-/-) and NF-kappaB1(-/-) mice but failed to detect PP in NF-kappaB2(-/-) mice. Whole-mount in situ hybridization revealed the presence of interleukin-7 receptor-alpha spots in NF-kappaB2(-/-) mice, indicating no defect in PP organogenesis of NF-kappaB2(-/-) mice in principle. Immunostaining shows that residual lymphocytes mainly consist of T cells. B cells are substantially reduced and are accumulated as terminal extravasations. Organized follicular structures and follicular dendritic cell networks fail to form, and myeloid, but not lymphoid, dendritic cells are obviously reduced. Expression of the chemokines macrophage inflammatory protein-3alpha, B-lymphocyte chemoattractant, and thymus-expressed chemokine is impaired in epithelial cells and in the subendothelial dome area that is not well defined. A similar but less severe phenotype is seen in Bcl-3(-/-) mice, which also do not develop germinal centers. In contrast, in NF-kappaB1(-/-) mice, T-cell numbers are visibly reduced, and no alteration could be observed in the B-cell and dendritic-cell populations. CONCLUSIONS: These data show that all 3 genes are crucial for PP development but contribute differently to PP organogenesis.

Adaptor Proteins, Signal Transducing↗