| 1. |
- Boström, Hans, et al.
(författare)
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PDGF-A/PDGF alpha-receptor signaling is required for lung growth and the formation of alveoli but not for early lung branching morphogenesis
- 2002
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Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 223:1, s. 155-162
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factors (PDGF) constitute a family of four gene products (PDGF-A-D) acting by means of two receptor tyrosine kinases, PDGFR alpha and beta. Three of the ligands (PDGF-A, -B, and -C) bind to PDGFR alpha with high affinity. Knockout of pdgf-a in mice has demonstrated a role for PDGF-A in the recruitment of smooth muscle cells to the alveolar sacs and their further compartmentalization into alveoli. Although this is a late, postnatal step in lung development, pdgf-a antisense oligonucleotides were previously shown to inhibit epithelial branching in rat lung explants in vitro, which reflects an early embryonic process. These conflicting results may be explained by substitution of genetic loss of pdgf-a by maternal transfer of PDGF-A to the knockout embryo or the presence of other PDGFR alpha agonists (PDGF-B and -C) in vivo, potentially masking an effect of PDGF-A on branching morphogenesis. Alternatively, the administration of pdgf-a antisense oligonucleotides affected other processes than the intended. To discriminate between these opposing possibilities, we have analyzed lung development in pdgfr alpha -/- embryos and lung primordia grown in vitro. Our analysis shows that, while the pdgfr alpha -/- lungs and explanted lung rudiments were smaller than normal, branching morphogenesis appears qualitatively intact and proceeds until at least embryonic day 15.5, generating both prospective conducting and respiratory airways. We conclude that, although PDGF-AA signaling over PDGFR alpha may have direct or indirect roles in overall lung growth, it does not specifically control early branching of the lung epithelium.
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| 2. |
- Fried, K., et al.
(författare)
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Expression of ErbB3, ErbB4, and neuregulin-1 mRNA during tooth development
- 2002
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Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 224:3, s. 356-360
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Tidskriftsartikel (refereegranskat)abstract
- The receptor tyrosine kinases ErbB3 and ErbB4, which bind to various variants of neuregulin (NRG), play fundamental roles in neural development and in organs, which form through epithelial-mesenchymal interactions. Here, we demonstrate that NRG-1 and the receptors ErbB3 and ErbB4 are expressed locally during rodent tooth development. However, the mRNA expression patterns of ErbB3 and ErbB4 were distinctly different during odontogenesis. Examinations of teeth in genetically heart-rescued ErbB4-/- mice did not reveal any obvious deviation from the normal phenotype. The results suggest that ErbB3 and ErbB4 may participate in tooth morphogenesis. The specific interactions between NRG isoforms and ErbB receptors during this process remain to be determined.
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| 3. |
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| 4. |
- Hart, Alan, et al.
(författare)
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Fgf10 maintains notch activation, stimulates proliferation, and blocks differentiation of pancreatic epithelial cells.
- 2003
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Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 228:2, s. 185-193
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Tidskriftsartikel (refereegranskat)abstract
- The pancreas is an endodermally derived organ that initially appears as a dorsal and ventral protrusion of the primitive gut epithelium. The pancreatic progenitor cells present in these early pancreatic anlagen proliferate and eventually give rise to all pancreatic cell types. The fibroblast growth factor receptor (FGFR) 2b high-affinity ligand FGF10 has been linked to pancreatic epithelial cell proliferation, and we have shown previously that Notch signalling controls pancreatic cell differentiation by means of lateral inhibition. In the developing pancreas, activated intracellular Notch appears to be required for maintaining cells in the progenitor state, in part by blocking the expression of the pro-endocrine gene neurogenin 3 (ngn3), and hence endocrine cell differentiation. Here, we show that persistent expression of Fgf10 in the embryonic pancreas of transgenic mice also inhibits pancreatic cell differentiation, while stimulating pancreatic epithelial cell proliferation. We provide evidence that one of the effects of the persistent expression of Fgf10 in the developing pancreas is maintained Notch activation, which results in impaired expression of ngn3 within the pancreatic epithelium. Together, our data suggest a role for FGF10/FGFR2b signalling in regulation of pancreatic cell proliferation and differentiation and that FGF10/FGFR2b signalling affects the Notch-mediated lateral inhibition pathway.
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| 5. |
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| 6. |
- Jaskoll, T., et al.
(författare)
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Sonic hedgehog signaling plays an essential role during embryonic salivary gland epithelial branching morphogenesis
- 2004
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Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 229:4, s. 722-732
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Tidskriftsartikel (refereegranskat)abstract
- Gene targeting studies indicate that sonic hedgehog (Shh) signaling plays an essential role during craniofacial development. Because numerous mandibular derivatives (e.g., teeth, tongue, Meckel's cartilage) are absent in Shh null mice and the embryonic submandibular salivary gland (SMG) develops from the mandibular arch, we postulated that Shh signaling is important for embryonic SMG development. To address this question, we first determined the spatiotemporal distribution of Shh; two transmembrane proteins, patched 1 (Ptc) and Smoothened (Smo), which act as a negative or a positive regulator of the Shh signal, respectively; and the Gli 3 transcription factor, which is downstream of the Shh signal. The epithelial localization of Shh, Ptc, Smo, and Gli 3 suggests that Shh signaling may act within the epithelium in a juxtacrine manner. The SMG phenotype in our embryonic day (E) 18.5 Shh null mice can be characterized as "paedomorphic," that is, it fails to progress to ontogenic stages beyond the Early Pseudoglandular (similar toE14). In a complementary set of experiments, we used organ culture to evaluate the effect of enhanced or abrogated Shh signaling on embryonic SMG development in vitro. Paired Ell 3 (Late Initial Bud stage) or E14 (Pseudogiandular stage) SMGs were cultured in the presence or absence of exogenous Shh peptide supplementation; Shh-supplemented explants exhibit a significant stage-dependent increase in branching morphogenesis compared with control explants. Furthermore, by using cyclopamine, a steroidal alkaloid that specifically disrupts the Shh pathway, to abrogate endogenous Shh signaling in vitro, we found a significant decrease in branching in cyclopamine-treated explants compared with controls, as well as a significant decrease in epithelial cell proliferation. Our results indicate that Shh signaling plays an essential role during embryonic SMG branching morphogenesis. Exogenous FGF8 peptide supplementation in vitro, rescues the abnormal SMG phenotype seen in cyclopamine-treated explants, demonstrating that overexpression of a parallel, but related, downstream signaling pathway can compensate for diminished Shh signaling and restore embryonic SMG branching morphogenesis. (C) 2004 Wiley-Liss, Inc.
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| 7. |
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| 8. |
- Landgren, Henrik, 1978, et al.
(författare)
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FoxJ3, a novel mammalian forkhead gene expressed in neuroectoderm, neural crest, and myotome
- 2004
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Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 231:2, s. 396-401
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Tidskriftsartikel (refereegranskat)abstract
- Forkhead transcription factors are important regulators of animal development. Here, we describe the embryonic expression pattern for one of the novel forkhead genes that were discovered as a result of the mouse and human genome projects. It is most closely related to FoxJ2 and has been assigned the name FoxJ3. The 100-kb, 13-exon mouse Foxj3 gene on chromosome 4 encodes a 623 amino acid (aa) protein from an mRNA of at least 4.8 kb (Human FOXJ3: Chr 1, 627 aa, 5.3-kb mRNA). During the stages of mouse development investigated (embryonic day [E] 8.5-E12.5) Foxj3 is expressed in neuroectoderm, in neural crest, and in many structures derived from neural crest cells, such as facioacoustic, trigeminal, and dorsal root ganglia. Stripes of expression appear at E10.5 in the location of myotomes and expand ventrally in a pattern similar to the developing body wall musculature. Developing limbs have a complex pattern of Foxj3 expression that at E12.5 colocalizes with the condensed mesenchyme of the skeletal primordia. (C) 2004 Wiley-Liss, Inc.
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| 9. |
- Lopes, SMCDS, et al.
(författare)
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Connective tissue growth factor expression and Smad signaling during mouse heart development and myocardial infarction
- 2004
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Ingår i: Developmental Dynamics. - : Wiley. - 1097-0177 .- 1058-8388. ; 231:3, s. 542-550
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Tidskriftsartikel (refereegranskat)abstract
- Connective tissue growth factor (CTGF) is reported to be a target gene of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) in vitro. Its physiological role in angiogenesis and skeletogenesis during mouse development has been described recently. Here, we have mapped expression of CTGF mRNA during mouse heart development, postnatal adult life, and after experimental myocardial infarction. Furthermore, we investigated the relationship between CTGF and the BMP/TGFbeta signaling pathway in particular during heart development in mutant mice. Postnatally, CTGF expression in the heart became restricted to the atrium. Strikingly, 1 week after myocardial infarction, when myocytes have disappeared from the infarct zone, CTGF and TGFbeta expression as well as activated forms of TGFbeta but not BMP, Smad effector proteins are colocalized exclusively in the fibroblasts of the scar tissue, suggesting possible cooperation between CTGF and TGFbeta, during the pathological fibrotic response. (C) 2004 Wiley-Liss, Inc.
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| 10. |
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| 11. |
- Ormestad, Mattias, 1974, et al.
(författare)
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Differences in the embryonic expression patterns of mouse Foxf1 and -2 match their distinct mutant phenotypes
- 2004
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Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 229:2, s. 328-333
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Tidskriftsartikel (refereegranskat)abstract
- Murine genes encoding the forkhead transcription factors Foxf1 and -2 are both expressed in derivatives of the splanchnic mesoderm, i.e., the mesenchyme of organs derived from the primitive gut. In addition, Foxf2 is also expressed in limbs and the central nervous system. Targeted mutagenesis of Foxf1 and -2 suggests that Foxf1 is the more important of the two mammalian FoxF genes with early embryonic lethality of null embryos and a haploinsufficiency phenotype affecting foregut-derived organs. In contrast, the only reported defect in Foxf2 null embryos is cleft palate. To investigate if the differences in mutant phenotype can be attributed to nonoverlapping expression patterns or if distinct functions of the encoded proteins have to be inferred, we analyzed the early embryonic expression of Foxf2 and compared it with that of the better investigated Foxf1. We find that in the early embryo, Foxf1 is completely dominating-in terms of expression-in extraembryonic and lateral plate mesoderm, consistent with the malformations and early lethality of Foxf1 null mutants. Along the developing gut, Foxf1 is highly expressed throughout, whereas Foxf2 expression is concentrated to the posterior part-fitting the foregut haploinsufficiency phenotypes of Foxf1 mutants. Foxf2, on the other hand, is more prominent than Foxf1 in mesenchyme around the oral cavity, as would be predicted from the cleft palate phenotype. The differences in expression pattern also highlight areas where defects should be sought for in the Foxf2 mutant, for example limbs, the posterior gut, genitalia, and derivatives of the neural crest mesenchyme.
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| 12. |
- Singh, Umashankar, et al.
(författare)
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Different Molecular Mechanisms Underlie Placental Overgrowth Phenotypes Caused by Interspecies Hybridization, Cloning, and Esx1 Mutation
- 2004
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Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 230:1, s. 149-164
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Tidskriftsartikel (refereegranskat)abstract
- To obtain a deeper insight into the genes and gene networks involved in the development of placentopathies, we have assessed global gene expression in three different models of placental hyperplasia caused by interspecies hybridization (IHPD), cloning by nuclear transfer, and mutation of the Esx1 gene, respectively. Comparison of gene expression profiles of approximately 13,000 expressed sequence tags (ESTs) identified specific subsets of genes with changed expression levels in IHPD, cloned, and Esx1 mutant placentas. Of interest, only one gene of known function and one EST of unknown function were found common to all three placentopathies; however, a significant number of ESTs were common to IHPD and cloned placentas. In contrast, only one gene was shared between IHPD and Esx1 mutant, and cloned and Esx1 mutant placentas, respectively. These genes common to different abnormal placental growth genotypes are likely to be important in the occurrence of placentopathy.
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| 13. |
- Yaneza, May, et al.
(författare)
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No evidence for ventrally migrating neural tube cells from the mid- and hindbrain.
- 2002
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Ingår i: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 223:1, s. 163-7
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Tidskriftsartikel (refereegranskat)abstract
- Abstract The neural crest is a migratory population of cells that originates from the dorsal neural tube in vertebrates. Recently, the existence of a group of ventrally emigrating neural tube (VENT) cells has been proposed, based upon cell labelling studies in the hindbrain of avian embryos. Like crest cells, these VENT cells have been reported to give rise to numerous cell types. VENT cell emigration is thought to occur after embryonic day (E) 3, when neural crest cell production has ceased. Migration of cells from the ventral neural tube into the periphery was inferred retrospectively after examining numerous embryos harvested at different stages. We have attempted to label VENT cells in vivo by using a green fluorescent protein (GFP) expression vector, electroporated into the ventral neural tube after crest cell migration and before the putative migration of the ventrally localised cells. Because GFP can be visualised strongly in living tissue a few hours after electroporation, the migration of labelled cells within the same embryo can be followed. Fluorescent cells labelled in the mid-hindbrain region were examined in ovo and in explant culture. No GFP-expressing cells were detected emigrating from the ventral neural tube from E3 to E5. Our findings are, thus, in disagreement with those of previous studies, which have indicated the existence of VENT cells in the cranial region.
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| 14. |
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