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At least 19 recordsLinked to original sources

Effects of polyamines on organogenesis and somatic embryogenesis of Lycium barbarum calli.

Levels of three endogenous free polyamines (PAs), Put, Spd and Spm, were detected during organogenesis and somatic embryogenesis (SE) of Lycium barabrum (L.) calli. The predominant forms of PAs in organogenesis and SE were found to be Put and Spd, respectively. In both developmental pathways, the changes of Put content were very similar, i.e., it accumulated quickly in the initial stages of calli differentiation and then decreased; with the further morphogenesis, increase in Put level was also observed. The highest level of Spd was obtained at day 1 of calli organogenesis; while, after 1 day of culture for calli SE, Spd level began to increase and reached a maximum at day 10. The treatments with exogenous PAs had positive effects on both organogenesis and SE, especially those of Spd on organogenesis and SE and Put on SE. However, Put showed no effects on adventitious bud formation. CHA, which inhibits the activity of Spd synthetase, prevented both adventitious bud formation and further development of somatic embryo into plantlet. Although MGBG, a specific inhibitor of S-adenosyl methionine decarboxylases, had little effects on organogenesis, it reduced the number of somatic embryo and the plantlets subsequently regenerated. Such inhibitions could be reversed by Spd (50 mumol/L). These results from organogenesis and SE of the same specie indicate that PAs influenced these two in vitro morphogenesis pathways.

Lycium↗

Co-expression of the HGF/SF and c-met genes during early mouse embryogenesis precedes reciprocal expression in adjacent tissues during organogenesis.

Early experiments with cells in culture and recent targeting experiments have confirmed that the mesenchyme-derived growth factor hepatocyte growth factor/scatter factor (HGF/SF) is a paracrine agent that regulates the development of several epithelial and myogenic precursor cells during organogenesis. Here, we report the expression pattern of HGF/SF and its receptor, the product of the proto-oncogene c-met, during gastrulation and early organogenesis in mouse embryo. During gastrulation, the expression of HGF/SF and c-met overlaps. Initially the two genes are expressed in the endoderm and in the mesoderm along the rostro-intermediate part of the primitive streak and, later, in the node and in the notochord. Neither HGF/SF nor c-met is expressed in the ectodermal layer throughout gastrulation. During early organogenesis, overlapping expression of HGF/SF and c-met is found in heart, condensing somites and neural crest cells. However, a second and distinct pattern of expression, characterized by the presence of the ligand in mesenchymal tissues and the receptor in the surrounding ectoderm, is seen in the bronchial arches and in the limb buds. At 13 days postcoitum (d.p.c.), only this second pattern of expression is observed in differentiated somites and several major organs (i.e., lungs, liver, and gut). The expression of the HGF/SF and c-met genes throughout embryogenesis suggests a shift from an autocrine to a paracrine signaling system. The shift takes place in early organogenesis and implies different roles of HGF/SF in development. During gastrulation, HGF/SF may affect the fate of migrating mesodermal cells and may play a role in axis determination, whereas during organogenesis, the expression patterns of HGF/SF and its receptor reflect the recently established roles in the growth of certain epithelia and the migration of specific myogenic precursor cells.

Animals↗

Stimulation of benzyladenine-induced in vitro shoot organogenesis and endogenous proline in melon (Cucumis melo L.) by fish protein hydrolysates in combination with proline analogues.

A previous study demonstrated that proline is beneficial for improving melon in vitro shoot organogenesis. A natural source of proline and proline precursors can be obtained from fish protein hydrolysates (FPH), a byproduct of the fishery industry. Proline analogues azetidine-2-carboxylate and hydroxyproline in combination with standardized FPH were used to stimulate proline synthesis and benzyladenine-induced shoot organogenesis by exploiting the proposed proline-linked pentose phosphate pathway (PPP). In the presence of elevated levels of endogenous proline, potential stimulation of cytokinins and auxin may occur via the PPP and shikimate pathways, respectively. Treatments with FPH singly and in combination with the above proline analogues significantly increased the endogenous proline content and the extent of differentiation, suggesting that in vitro organogenesis is closely linked to proline synthesis, strengthening the hypothesis that purine metabolism via the proline-linked PPP may be important for organogenesis. Thioproline addition resulted in increased proline levels but without corresponding stimulation of organogenesis. This study also provides potential use of fishery waste for value-added application in plant micropropagation industry.

Adenine↗

Abnormal organogenesis in salivary gland development may initiate adult onset of autoimmune exocrinopathy.

OBJECTIVES: Salivary gland organogenesis was evaluated in NOD mice, an animal model for autoimmune exocrinopathy, to determine when disease onset is first present in the target tissues. METHODS: Submandibular glands were removed for histological, immunohistochemical and biochemical evaluation from neonatal NOD and congenic strains as well as healthy control C57BL/6 mice. RESULTS: Histomorphological analyses of neonatal submandibular glands, the primary target for autoimmune exocrinopathy at 1 day postpartum, revealed delayed morphological differentiation during organogenesis in autoimmune-susceptible NOD mice when compared to nonsusceptible C57BL/6 mice. Acinar cell proliferation was reduced, while expression of Fas, FasL and bcl-2 were increased. Acinar cell proliferation was reduced, while expression, of Fas, FasL and bcl-2 were increased. Throughout the preweaning period (21 days) submandibular glands from NOD and NOD congenic strains aberrantly expressed an increased matrix metalloproteinase (MMP)-2 and MMP-9 activity. Substitution of two susceptibility alleles (Idd3 and Idd5) in NOD mice resulted in an hierarchical and additive reversal of delayed organogenesis, elevated MMP-9 activity, and aberrant expression of parotid secretory protein. DISCUSSION: NOD-derived mice whose submandibular glands showed normal organogenesis did not progress to develop autoimmune exocrinopathy. Altered organogenesis of target tissue may therefore provide a cellular microenvironment capable of activating autoimmunity.

Aging↗

A staging scheme for assessing development in vitro of organogenesis stage embryos of the stripe-faced dunnart, Sminthopsis macroura (Marsupialia: dasyuridae).

The inaccessibility of mammalian organogenesis stage embryos has precluded their widespread use in embryological and teratological studies. As organogenesis occurs during the last 1.5 days of the 10. 7 days of gestation in the stripe-faced dunnart (Sminthopsis macroura), the aim of the present study was to investigate whether day 9 and day 10 embryos and fetuses could be grown to term in vitro. High glucose Dulbecco's modified Eagle's medium with 10% fetal calf serum (FCS) supported embryonic growth for various periods of time, some to within 5 h of the predicted time of parturition. A roller culture system maintained at 35 degrees C was used to incubate organogenesis stage embryos (n = 43). Nine unincubated (control) embryos were either fixed for microscopic analysis or frozen for microprotein determination. The results of the present study indicate that with some optimization of the culture conditions (increasing oxygen in the gas phase in the culture tubes, replacing FCS with rat serum), it might be possible for organogenesis stage S. macroura embryos to be grown to term. A scoring scheme for assessing morphological development was devised for use as a standard in staging organogenesis stage embryos. This scheme reflects the highly compressed schedule of developmental events that occurs mainly during day 9 of gestation in S. macroura embryos. In comparison, during embryogenesis in Didelphis virginiana these developmental events occur from day 8 to day 10.5 of gestation, and birth occurs on day 13.

Animals↗

Studies of 50 Hz circularly polarized magnetic fields of up to 350 microT on reproduction and embryo-fetal development in rats: exposure during organogenesis or during preimplantation.

Groups of mated female Sprague-Dawley rats were simultaneously exposed to 0 (sham exposed), 7, 70, or 350 microT (rms) circularly polarized 50 Hz magnetic fields (MF) for 22 h/day on gestational day 8-15, the period of rat fetal organogenesis (organogenesis study) or from day 0 to day 7 of gestation, the rat preimplantation period (preimplantation study). Developmental toxicity was assessed on gestational day 20. Identical experiments were repeated to confirm reproducibility of both studies. In both studies, statistically significant differences between exposed and sham exposed animals were observed in several measured parameters; however, these differences only appeared in one, but not both replicate experiments and generally at only an isolated exposure level. Because these differences were not reproducible and did not show a dose response relationship, they were not considered related to MF exposure. In the organogenesis study, lower kidney weights of dams were seen at 70 and 350 microT in Experiment 1. Lower dam liver weights and lower mean body weights of viable female and male fetuses were seen at 70 microT in Experiment 2. Otherwise, there were no differences in these parameters or in group means for fetal loss after implantation, number of viable fetuses, fetal body weight and sex ratio, incidences of external, visceral, and skeletal abnormalities or variations, or tissue abnormalities after histopathological examination. In the preimplantation study, dam health and indices for reproduction and embryo-fetal development, including pre or postimplantation loss, number and body weight of live fetuses, and sex ratio, external, skeletal abnormalities and variations, and skeletal ossification did not differ. Dam inorganic phosphorous concentration at 350 microT was elevated in one experiment and depressed in another. In one experiment, visceral abnormalities, primarily thymic remnant in neck and accessory liver lobe, were increased in the 7 microT group. Based on these results from two studies, we conclude that circularly polarized 50 Hz MF exposure of up to 350 microT during the fetal organogenesis or during the preimplantation period does not affect reproduction and embryo-fetal development in Sprague-Dawley rats.

Animals↗

Coordinated control of cell adhesion, polarity, and cytoskeleton underlies Hox-induced organogenesis in Drosophila.

BACKGROUND: Hox genes control animal body plans by directing the morphogenesis of segment-specific structures. As transcription factors, HOX proteins achieve this through the activation of downstream target genes. Much research has been devoted to the search for these targets and the characterization of their roles in organogenesis. This has shown that the direct targets of Hox activation are often transcription factors or signaling molecules, which form hierarchical genetic networks directing the morphogenesis of particular organs. Importantly, very few of the direct Hox targets known are "realizator" genes involved directly in the cellular processes of organogenesis. RESULTS: Here, we describe for the first time a complete network linking the Hox gene Abdominal-B to the realizator genes it controls during the organogenesis of the external respiratory organ of the larva. In this process, Abdominal-B induces the expression of four intermediate signaling molecules and transcription factors, and this expression results in the mosaic activation of several realizator genes. The ABD-B spiracle realizators include at least five cell-adhesion proteins, cell-polarity proteins, and GAP and GEF cytoskeleton regulators. Simultaneous ectopic expression of the Abd-B downstream targets can induce spiracle-like structure formation in the absence of ABD-B protein. CONCLUSION: Hox realizators include cytoskeletal regulators and molecules required for the apico-basal cell organization. HOX-coordinated activation of these realizators in mosaic patterns confers to the organ primordium its assembling properties. We propose that during animal development, Hox-controlled genetic cascades coordinate the local cell-specific behaviors that result in organogenesis of segment-specific structures.

Animals↗

Organogenesis of peripheral lymphoid organs.

The discovery that lymphotoxin alpha (LTalpha) knockout mice lack peripheral lymphoid tissues reformed the study of organogenesis of peripheral lymphoid tissues from a research field that was solely descriptive and dependent on histological methods to one requiring all modern technologies. The concepts of inducer cells for organogenesis of peripheral lymphoid tissues as a separate hematopoietic lineage and of mesenchymal organizer cells have been established through this progress. These discoveries led to the comprehension of the basic framework of the events during organogenesis of peripheral lymphoid tissues. However, many important questions remain unanswered. This review discusses those questions which have arisen from our studies on the organogenesis of Peyer's patches.

Animals↗

Thidiazuron induces shoot organogenesis at low concentrations and somatic embryogenesis at high concentrations on leaf and petiole explants of African violet (Saintpaulia ionantha Wendl).

Regeneration via shoot organogenesis and somatic embryogenesis was observed from thidiazuron (TDZ)-treated leaf and petiole explants of greenhouse- and in vitro-grown African violet plants. The response of cultures to other growth regulators over a range of 0.5 microM to 10 microM was 50% less than that observed with TDZ. A comparative study among several cultivars of African violet indicated that "Benjamin" and "William" had the highest regeneration potential. In "Benjamin", higher frequencies of shoot organogenesis (twofold) and somatic embryogenesis (a 50% increase) were observed from in vitro- and greenhouse-grown plants, respectively. At concentrations lower than 2.5 microM, TDZ induced shoot organogenesis, whereas at higher doses (5-10 microM) somatic embryos were formed. These findings provide the first report of simultaneous shoot organogenesis and somatic embryogenesis of African violet explants in response to TDZ.

Culture Techniques↗

Regulation of the Yp subunit of glutathione S-transferase P in rat embryos and yolk sacs during organogenesis.

Manipulation of the glutathione status of an embryo during organogenesis leads to abnormal development, as well as increasing the susceptibility of the embryo to insult by either xenobiotic or endogenous electrophiles. The glutathione S-transferases are a family of drug-metabolizing enzymes that catalyze the conjugation of reactive chemicals with glutathione, playing an important role in protecting cells against attack. The purpose of this study was to investigate the presence and regulation of one glutathione S-transferase, glutathione S-transferase P, a homodimer of the Yp subunit, in the conceptus during organogenesis. Northern blot analysis of the RNA isolated from rat embryos and their yolk sacs on days 10, 11 and 12 of gestation revealed a single Yp transcript. Steady-state concentrations of the Yp mRNA in embryos did not change with either gestational age or culture for 24 hr (day 11 in vitro) or 45 hr (day 12 in vitro). In contrast, concentrations of this transcript in yolk sac increased 3-fold from day 10 to 12 of gestation and a further 3-fold with culture (day 12 in vivo compared with in vitro). Transcription of the rat Yp subunit gene in cell lines is induced by treatment with phorbol esters. However, the addition of 12-O-tetradecanoylphorbol-13-acetate (TPA, 50 or 100 nM) to embryos in culture had no effect on the steady-state concentrations of the Yp transcript. Thus, the glutathione S-transferase Yp message is subject to tissue- and development-specific regulation in the conceptus during organogenesis. Moreover, culture of the embryos resulted in a further up-regulation of the steady-state concentrations of the Yp transcript in yolk sac. Western blot analysis demonstrated that a single immunoreactive Yp subunit band of 26 kDa was found in both embryos and yolk sacs. Neither age nor culture appeared to affect the concentrations of immunoreactive Yp subunit in the yolk sac. Thus, glutathione S-transferase Yp mRNA is translated in the conceptus during organogenesis. The apparent differences between the relative amounts of the message and immunoreactive protein in yolk sac suggest that this subunit may be subject to post-transcriptional as well as transcriptional regulation in this tissue. Immunohistochemical analysis of embryos cultured for 45 hr (day 12 in vitro) revealed that the Yp reaction product was localized over the hepatic primordia, mesonephric ducts, otocyst, yolk sac and ectoplacental cone.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Peyer's patch organogenesis as a programmed inflammation: a hypothetical model.

Gene-knock-out studies implicate roles of lymphotoxin (LT) alphabeta and LT betaR in the initial phase of Peyer's patch (PP) organogenesis. We recently identified the requirement of IL-7R alpha/gamma c/Jak3 signal in LT alphabeta production of IL-7R alpha+ cells. These observations lead us to a hypothetical model for PP organogenesis with three cellular components. The first is the producer of the ligand for IL-7R alpha, which then stimulate the IL-7R alpha+ cells to produce LT alphabeta activating the LT betaR+ cells to form an organizing center for PP organogenesis. This model is similar to that of inflammation, suggesting that PP organogenesis is a programmed version of inflammation.

Animals↗

The role of maternally derived epidermal growth factor and the epidermal growth factor receptor during organogenesis in the rat embryo.

Epidermal growth factor (EGF) has been implicated in the control of embryonic development, but although the receptor is expressed from an early stage, there is little evidence of embryonic expression of EGF. In order to investigate the role of maternally derived EGF during organogenesis, rat embryos were explanted at d 9.5 and cultured in serum depleted of low molecular weight molecules (retenate) which was then supplemented with EGF. Serum depleted of low molecular weight molecules by prolonged filtration loses its capacity to support normal embryonic development, possibly due to the loss of growth promoting factors. The addition of EGF to retenate significantly improved embryonic development with a maximal effect at 8 ng/ml. The addition of an analogue of EGF, long EGF, to retenate also caused a significant increase in development, although at higher concentrations a decrease in its effect was observed, possibly due to down regulation of the EGF receptor. Therefore, embryos may be able to utilise maternally derived EGF during organogenesis. To test the effects of inhibiting the EGF receptor during organogenesis, d 9.5 embryos were cultured in the presence of tyrphostin 47, a specific EGF receptor inhibitor. Tyrphostin 47 caused a significant dose-dependent decrease in the development of embryos which was also observed when tyrphostin 47 was injected into the vitelline circulation at d 11.5 to bypass the effects of the yolk sac. These findings suggest that the EGF receptor is essential for normal organogenesis and may play a role in the control of proliferation and differentiation. Although EGF is not expressed in the rat embryo at this stage, maternally derived EGF may be the ligand for the embryonic EGF receptor.

Animals↗

Peyer's patch organogenesis is intact yet formation of B lymphocyte follicles is defective in peripheral lymphoid organs of mice deficient for tumor necrosis factor and its 55-kDa receptor.

Targeted inactivation of genes in the tumor necrosis factor (TNF)/lymphotoxin (LT) ligand and receptor system has recently revealed essential roles for these molecules in lymphoid tissue development and organization. Lymphotoxin-alphabeta (LTalphabeta)/lymphotoxin-beta receptor (LTbeta-R) signaling is critical for the organogenesis of lymph nodes and Peyer's patches and for the structural compartmentalization of the splenic white pulp into distinct B and T cell areas and marginal zones. Moreover, an essential role has been demonstrated for TNF/p55 tumor necrosis factor receptor (p55TNF-R) signaling in the formation of splenic B lymphocyte follicles, follicular dendritic cell networks, and germinal centers. In contrast to a previously described essential role for the p55TNF-R in Peyer's patch organogenesis, we show in this report that Peyer's patches are present in both TNF and p55TNF-R knockout mice, demonstrating that these molecules are not essential for the organogenesis of this lymphoid organ. Furthermore, we show that in the absence of TNF/p55TNF-R signaling, lymphocytes segregate normally into T and B cell areas and a normal content and localization of dendritic cells is observed in both lymph nodes and Peyer's patches. However, although B cells are found to home normally within Peyer's patches and in the outer cortex area of lymph nodes, organized follicular structures and follicular dendritic cell networks fail to form. These results show that in contrast to LTalphabeta signaling, TNF signaling through the p55TNF-R is not essential for lymphoid organogenesis but rather for interactions that determine the cellular and structural organization of B cell follicles in all secondary lymphoid tissues.

Animals↗

Peyer's patch organogenesis--cytokines rule, OK?

Targeted inactivation of genes in the tumor necrosis factor (TNF)/lymphotoxin (LT) ligand and receptor system has recently revealed essential roles forthese molecules in lymphoid tissue development and organization. Lymphotoxin-alpha beta (LT alpha beta)/lymphotoxin-beta receptor (LT beta-R) signaling is critical for the organogenesis of lymph nodes and Peyer's patches and for the structural compartmentalization of the splenic white pulp into distinct B and T cell areas and marginal zones. Moreover, an essential role has been demonstrated for TNF/p55 tumor necrosis factor receptor (p55TNF-R) signaling in the formation of splenic B lymphocyte follicles, follicular dendritic cell networks, and germinal centers. In contrast to a previously described essential role for the p55TNF-R in Peyer's patch organogenesis, we show in this report that Peyer's patches are present in both TNF and p55TNF-R knockout mice, demonstrating that these molecules are not essential for the organogenesis of this lymphoid organ. Furthermore, we show that in the absence of TNF/p55TNF-R signaling, lymphocytes segregate normally into T and B cell areas and a normal content and localization of dendritic cells is observed in both lymph nodes and Peyer's patches. However, although B cells are found to home normally within Peyer's patches and in the outer cortex area of lymph nodes, organized follicular structures and follicular dendritic cell networks fail to form. These results show that in contrast to LT alpha beta signaling, TNF signaling through the p55TNF-R is not essential for lymphoid organogenesis but rather for interactions that determine the cellular and structural organization of B cell follicles in all secondary lymphoid tissues.

Animals↗

Involvement of distinct cellular compartments in the abnormal lymphoid organogenesis in lymphotoxin-alpha-deficient mice and alymphoplasia (aly) mice defined by the chimeric analysis.

Both lymphotoxin-alpha (LTalpha)-deficient mice and alymphoplasia (aly) mice, a natural mutant strain, manifest a quite similar phenotype: lack of lymph nodes (LN) and Peyer's patches (PP), with disturbed spleen architecture. The mechanisms underlying the defective lymphoid organogenesis in these mice were investigated by generating aggregation chimeras; ex vivo fused morulae were implanted into pseudo-pregnant host females and allowed to develop to term. Chimeric mice between LTalpha-deficient mice and wild-type mice restored LN and PP almost completely, suggesting that LTalpha expressed by circulating bone marrow-derived cells is essential for lymphoid organogenesis as well as for organization of spleen architecture. By contrast, chimeric mice between aly mice and wild-type mice showed only limited restoration of LN and PP. This suggests that the putative aly gene product does not act as a circulating ligand for lymphoid organogenesis, like LTalpha. Rather, abnormal development of lymphoid organs in aly mice seems most likely due to the defective development of the incipient stromal cells of the LN and PP. Supporting this hypothesis, up-regulation of VCAM-1 on aly mouse embryonic fibroblasts by signals through LTbetaR, which is exclusively expressed by nonlymphoid cells, was disturbed. These studies demonstrate that LTalpha and the putative aly gene product together control lymphoid organogenesis with a close mechanistic relationship in their biochemical pathways through governing the distinct cellular compartments, the former acting as a circulating ligand and the latter as a LTbetaR-signaling molecule expressed by the stroma of the lymphoid organs.

Animals↗

Role of TNF ligand and receptor family in the lymphoid organogenesis defined by gene targeting.

The molecular basis of lymphoid organogenesis has recently been elucidated using gene-targeted mice. Mice deficient in lymphotoxin-alpha (LT alpha) lack lymph nodes and Peyer's patches. The action of LT alpha in lymphoid organogenesis is mediated mostly by the membrane form of LT by a mechanism independent of TNF receptor I (TNFR-I) or II (TNFR-II). Additionally, follicular dendritic cell (FDC) clusters or germinal centers fail to develop in the spleen of LT alpha-deficient mice. Mice deficient in either TNFR-I or LT beta R also fail to develop splenic FDC clusters and germinal centers, indicating that signaling through both TNFR-I and LT beta R is required for the development of these structures. The mechanisms underlying the defective lymphoid organogenesis in LT alpha-deficient mice, together with a natural mutant strain, alymphoplasia (aly) mice, which manifest a quite similar phenotype to LT alpha-deficient mice, were investigated by generating aggregation chimeras. These studies demonstrate that LT alpha and the aly gene product together control lymphoid organogenesis with a close mechanistic relationship in their biochemical pathways through governing distinct cellular compartments; the former acting as a circulating ligand and the latter as a LT beta R-signaling molecule expressed by the stroma of the lymphoid organs.

Animals↗

Rat embryos express transcripts for cyclooxygenase-1 and carbonic anhydrase-4, but not for cyclooxygenase-2, during organogenesis.

BACKGROUND: Acetylsalicylic acid (ASA) is a rat teratogen, and exposures on gestational days (GDs) 9 and 10 induce diaphragm, cardiac, and midline defects. ASA inhibits members of the cyclooxygenase (COX) family and potentially members of the carbonic anhydrase (CA) family. The objective of this study was to determine whether the mRNA developmental expression pattern for any COX or CA isoform was consistent with a model in which ASA teratogenicity is mediated through direct interaction with one of these enzymes within embryos or within the adjacent ectoplacental cone (EPC) or yolk sac. METHODS: Staged embryos, over a range (GD 9.5-12) that included ASA-sensitive and ASA-insensitive stages of organogenesis, were assayed for COX and CA mRNA levels by three techniques: microarrays; in situ hybridization quantitated by a micro-imager; and quantitative reverse transcription polymerase chain reaction. ASA- and vehicle-treated embryos also were compared to determine whether inhibition led to upregulated COX or CA mRNA expression. RESULTS: COX-2 mRNA was undetectable in embryos throughout organogenesis by any assay (although it was abundant in EPC). In contrast, COX-1 mRNA was moderately abundant in embryos throughout organogenesis. One CA isoform, CA-4, demonstrated developmentally regulated embryonic mRNA expression that coincided with ASA sensitivity ASA exposure failed to induce upregulation of any of these mRNAs. CONCLUSIONS: Although ASA may affect the embryo indirectly through interaction with COX-2 within EPC, failure to detect embryonic COX-2 mRNA argues against COX-2 functioning as a direct mediator of ASA teratogenic activity in induction of cardiac, diaphragm, and midline defects. Correlation of COX-1 and CA-4 expression with ASA sensitivity suggested that embryonic COX-1 and possibly CA4 are much more likely candidates for mediators of ASA developmental toxicity.

Animals↗

Spatio-temporal expression of Pbx3 during mouse organogenesis.

Pbx3 is a member of the Pbx family of TALE (three amino acid loop extension) class homeodomain transcription factors. These transcription factors are implicated in developmental and transcriptional gene regulation in numerous cell types through their abilities to form hetero-oligomeric DNA-binding complexes. Pbx3 was found to be expressed at high levels in the developing central nervous system (CNS), including a region of the medulla oblongata which is implicated in the control of respiration. Furthermore, as reported, Pbx3-deficient mice develop to term but die within a few hours of birth from central respiratory failure. In this study, we have characterized Pbx3 expression patterns during organogenesis in numerous tissues and organ systems other than the CNS, as a first step toward understanding the potentially overlapping functions of Pbx3 with other Pbx family members during vertebrate development. We have performed in situ hybridization on whole mount and sectioned mouse embryos from gestational day (E) 9 to E16.5. During early organogenesis, until E12.5, Pbx3 expression is found mostly in the embryonic head, forelimbs, and septum transversum, unlike Pbx1 and Pbx2 expression which is more widespread. Conversely, later in organogenesis, Pbx3 expression becomes more widely detectable throughout the developing embryo. Epithelial and mesenchymal tissues, as well as the CNS, represent major sites of Pbx3 expression. The enteric nervous system also expresses high levels of Pbx3, distinctively in the cells of the ganglia of Auerbach's myenteric nerve plexus, that also express Dlx2 and Notch1. Cartilage is also a site of Pbx3 expression. Interestingly, like Pbx1, Pbx3 is highly expressed in proliferating chondrocytes but is lost as chondrocytes become hypertrophic during endochondral ossification. Finally, Pbx3 is expressed only in the forelimb buds during early limb development, while the hindlimb bud is devoid of Pbx3. This finding leads us to add Pbx3 to the sparse list of early forelimb-specific molecular markers.

Animals↗