bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fgf10 maintains notch activation, stimulates proliferation, and blocks differentiation of pancreatic epithelial cells
Authors: Hart Alan , Papadopoulou Stella , Edlund Helena 
Published: September 2003

AbstractThe 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. Developmental Dynamics 228:185–193, 2003. © 2003 Wiley‐Liss, Inc.
Growth/differentiation factor 5 enhances chondrocyte maturation
Authors: Coleman Cynthia M. , Tuan Rocky S. 
Published: September 2003

AbstractGrowth/differentiation factor 5 (GDF5) is required for limb mesenchymal cell condensation and joint formation during skeletogenesis. Here, we use a model consisting of long‐term, high‐density cultures of chick embryonic limb mesenchymal cells, which undergo the entire life history of chondrocyte development, to examine the effects of GDF5 overexpression on chondrocyte maturation. Exposure to GDF5 significantly enhanced chondrocyte hypertrophy and maturation, as determined by the presence of alkaline phosphatase activity, collagen type X protein production, and the presence of a sulfated proteoglycan‐rich extracellular matrix. Histologic analysis also revealed an increase in cell volume and cellular encasement in larger lacunae in GDF5‐treated cultures. Taken together, these results support a role for GDF5 in influencing chondrocyte maturation and the induction of hypertrophy in the late stages of embryonic cartilage development, and provide additional mechanistic insights into the role of GDF5 in skeletal development. Development Dynamics 228:208–217, 2003. Published 2003 Wiley‐Liss, Inc.
lunatic fringe regulates delta‐notch induction of hypochord in zebrafish
Authors: Appel Bruce , Marasco Paul , McClung Laura E. , Latimer Andrew J. 
Published: September 2003

AbstractCells that occupy the midline of vertebrate embryos arise from a common population of precursors. Several lines of evidence indicate that Delta‐Notch signaling regulates specification of midline precursors for different fates. We show that zebrafish midline precursors transiently express lunatic fringe, which encodes a glycosyltransferase that modifies Notch activity in response to its ligands, and that lunatic fringe function is required for Delta‐Notch–mediated induction of hypochord cells at the lateral borders of the midline precursor domain. Development Dynamics 228:281–286, 2003. © 2003 Wiley‐Liss, Inc.
Major role of BAX in apoptosis during retinal development and in establishment of a functional postnatal retina
Authors: Péquignot M.O. , Provost A.C. , Sallé S. , Taupin P. , Sainton K.M. , Marchant D. , Martinou J.C. , Ameisen J.C. , Jais J.‐P. , Abitbol M. 
Published: September 2003

AbstractApoptosis plays a major role in the development of the central nervous system. Previous studies of apoptosis induction during retinal development are difficult to interpret, however, because they explored different mouse strains, different developmental periods, and used different assays. Here, we first established a comprehensive sequential pattern of cell death during the whole development of the C57BL/6J mouse retina, from E10.5 to postnatal day (P) 21 by using the terminal deoxynucleotidyl transferase (TdT) ‐mediated deoxyuridine triphosphate (dUTP)–biotinylated nick end labeling (TUNEL) assay. We confirmed the existence of three previously described apoptotic peaks and identified another, later peak at P15, in both the outer nuclear layer, in which the photoreceptors differentiate, and the ganglion cell layer. Comparison of wild‐type C57BL/6 mice, gld mice, defective in the death ligand fasL, and bax‐/‐ mice, defective in the pro‐apoptotic BAX protein, revealed a minor role for FAS ligand but a crucial role for BAX in both apoptosis and normal retinal development. The lack of BAX resulted in thicker than normal inner neuroblastic and ganglion cell layers in adults, with larger numbers of cells and an impaired electroretinogram response related to a decreased number of responsive cells. Our findings indicate that cell death during normal retinal development is important for the modeling of a functional vision organ and showed that the pro‐apoptotic BAX protein plays a crucial role in this process. Developmental Dynamics 228:231–238, 2003. © 2003 Wiley‐Liss, Inc.
Involvement of hepatocyte growth factor in branching morphogenesis of murine salivary gland
Authors: Ikari Tatsuya , Hiraki Akimitsu , Seki Katsuhiro , Sugiura Tsuyoshi , Matsumoto Kunio , Shirasuna Kanemitsu 
Published: September 2003

AbstractWe investigated the involvement of hepatocyte growth factor (HGF) in salivary gland (SG) branching morphogenesis. The mouse submandibular gland (SMG) starts to develop at embryonic day 11.5–12 (E11.5–E12), and branching morphogenesis occurs in the area between the mandibular bone and tongue between E14 and E16.5. Real‐time reverse transcriptase‐polymerase chain reaction showed that the expression of the c‐met/HGF receptor gene in SMG increased and peaked between E14 and E16.5, concomitant with epithelial branching, and high levels of HGF mRNA were detected in the surrounding mesenchyme at E14–E15.5. Although strong expression of the HGF and c‐met transcripts was observed in the tongue muscles, this expression was limited at E13.5–E14.5. Serum‐free organ cultures were established, in which SG rudiments that contained SMG and sublingual gland (SLG) primordia (explant 1) and SMG/SLG rudiments with peripheral tissue that included part of the tongue muscle (explant 2) were isolated from E13.5 or E14 embryos. Mesenchyme‐free SMG epithelium was obtained by the removal of mesenchymal tissue from explant 1. In the explant 1 and 2 organ cultures, SMG/SLG rudiments showed growth and branching morphogenesis, while mesenchyme‐free epithelium failed to grow. When E13.5 or E14 mesenchyme‐free epithelium and a recombinant human HGF (rh‐HGF) ‐soaked bead were placed on Matrigel, the epithelium migrated toward the bead and formed branches, while the E13 epithelium failed to branch. The exogenous application of rh‐HGF and anti‐HGF antibody to the SMG/SLG rudiment cultures resulted in stimulation and inhibition, respectively, of branching morphogenesis. However, the response of E13.5 SMG to rh‐HGF was very weak, while the branching of E14 SMG was enhanced strongly by rh‐HGF. The branching morphogenesis of SMG was also inhibited by the addition of either antisense HGF or c‐met oligodeoxynucleotides to the cultures. The development of SMG in explant 2, which was significantly better than in explant 1, was comparable to that seen in vivo. Moreover, the expression of both HGF and c‐Met in the SMG of explant 2 was higher than in the SMG of explant 1. These findings provide the first demonstration that the branching morphogenesis of SMG is regulated by interactions with the surrounding mesenchyme‐derived HGF and c‐met expression in SMG, which occur concomitant with epithelial branching. The present data also suggest that the HGF that is released transiently from tongue muscles may contribute to the rapid development of SMG at the branching stage. Developmental Dynamics 228:173–184, 2003. © 2003 Wiley‐Liss, Inc.
Abundant and dynamic expression of G protein‐coupled P2Y receptors in mammalian development
Authors: Cheung Kwok‐Kuen , Ryten Mina , Burnstock Geoffrey 
Published: September 2003

AbstractExtracellular ATP mediates diverse biological effects by activating two families of receptors, the P2X and P2Y receptors. There is growing evidence to show that activation of G protein‐coupled P2Y receptors can produce trophic effects in many cell types. Yet the expression and function of the P2Y receptors in development has rarely been studied and has never been investigated in mammalian development. This study used the reverse transcription‐polymerase chain reaction and immunohistochemistry to demonstrate the abundant and dynamic expression of P2Y receptors in rat development. These receptors were expressed in a wide range of embryonic structures, notably somites, skeletal muscle, the central and peripheral nervous system, the heart, lung, and liver. All the P2Y receptors studied were expressed as early as embryonic day 11, when most embryonic organs were far from being functional and still in the process of being formed. P2Y receptor proteins were strongly expressed in temporary, developmental structures that do not have a correlate in the adult animal, including the somites (P2Y1, P2Y2, and P2Y4) and the floor plate of the neural tube (P2Y1). P2Y receptors were also dynamically expressed, with receptor mRNA and protein being both up‐ and down‐regulated at different developmental stages. The down‐regulation of the P2Y1, 2, and 4 receptor proteins in skeletal muscle and heart, and the disappearance of the P2Y4 receptor from the brainstem and ventral white matter of the spinal cord postnatally, demonstrated that many P2Y receptors were likely to be involved in functions specific to embryonic life. Thus, these findings strongly suggest that P2Y receptors play an important role in the development of many tissues, and pioneer further studies into the role of purinergic signalling in development. Developmental Dynamics 228:254–266, 2003. © 2003 Wiley‐Liss, Inc.
Regionally distinct potencies of mouse XY genital ridge to initiate testis differentiation dependent on anteroposterior axis
Authors: Hiramatsu Ryuji , Kanai Yoshiakira , Mizukami Takuo , Ishii Maki , Matoba Shogo , Kanai‐Azuma Masami , Kurohmaru Masamichi , Kawakami Hayato , Hayashi Yoshihiro 
Published: September 2003

AbstractIn mouse gonadal differentiation, the center‐to‐pole Sry expression pattern suggests the regionally distinct potencies of the genital ridge, which induce testis differentiation. In this study, we examined the anteroposterior axis‐dependent differences in testis‐differentiation potencies by using cultures of anterior, middle, and posterior segments of the XY genital ridge. The inducible pattern of Sertoli cell differentiation showed a center‐to‐pole wave similar to the initial Sry expression pattern. In contrast, the ability to induce Leydig cell differentiation emanated from the anterior segment and then spread to the posterior side. These findings suggest the presence of two distinct dynamic waves in the capacity of the genital ridge to induce Sertoli or Leydig cell differentiation at early phases of testis differentiation. Developmental Dynamics 228:247–253, 2003. © 2003 Wiley‐Liss, Inc.
Patterning of the hyoid cartilage depends upon signals arising from the ventral foregut endoderm
Authors: Ruhin Blandine , Creuzet Sophie , Vincent Christine , Benouaiche Laurence , Le Douarin Nicole M. , Couly Gérard 
Published: September 2003

AbstractHyoid bone is a part of the visceral skeleton which arises from both Hox‐expressing (Hox+) and Hox‐nonexpressing (Hox‐) cephalic neural crest cells. In a previous work, we have demonstrated that the Hox‐ neural crest domain behaves as a naïve entity to which the ventral foregut endoderm confers patterning cues to specify the shape and orientation of the nasal and mandibular skeleton. By using ablation and grafting approaches, we have extended our study to the formation of the hyoid bone and tested the patterning ability of more caudal levels of the lateroventral foregut endoderm in the chick embryo at the early neurula stage. In this study, endodermal stripes have first been delineated according to the projection of mid‐ and posterior rhombencephalic structures. The extirpation of endodermal transverse stripes along the anteroposterior axis selectively hampers the formation of the ceratobranchials and epibranchials. Thus defined, the patterning ability of the endodermal stripes was further explored in their medial and lateral parts. When homotopically engrafted on the migration pathway of cephalic neural crest cells, ventromedial zones of endoderm lead to the formation of supernumerary basihyal and basibranchial, while lateral zones generate additional cartilaginous pieces recognizable as ceratobranchial and epibranchial. Taken together, our data demonstrate that, early in development, the ventral foregut endoderm exerts a regionalized patterning activity on the cephalic neural crest to build up the primary facial and visceral skeleton in jaws and neck and enable a map of the endodermal skeletogenic areas to be drawn. This map reveals that a cryptic metamerization of the anterior foregut endoderm precedes the formation of the branchial arches. Developmental Dynamics 228:239–246, 2003. © 2003 Wiley‐Liss, Inc.
Molecular mechanisms of early gut organogenesis: A primer on development of the digestive tract
Authors: Kiefer Julie C. 
Published: September 2003

AbstractCreating an organ poses unique challenges in embryogenesis, including establishing an organ primordium and coordinating development of different tissues in the organ. The digestive tract (gut) is a complex organ system, posing the interesting question of how the development of a series of organs is coordinated to establish an organ system with a common function. Although gut development has been the focus of much research, the molecular mechanisms that regulate these events are just beginning to be understood. This primer will first outline the basic anatomy of the digestive tract and then focus on molecular mechanisms that drive vertebrate gut organogenesis. Deciphering mechanisms underlying gut organogenesis also provides insights into understanding the development of other organs. Developmental Dynamics 228:287–291, 2003. © 2003 Wiley‐Liss, Inc.
Effects of antisense misexpression of CFC on downstream flectin protein expression during heart looping
Authors: Linask Kersti K. , Han Ming‐Da , Linask Kaari L. , Schlange Thomas , Brand Thomas 
Published: September 2003

AbstractDextral looping of the heart is regulated on multiple levels. In humans, mutations of the genes CFC and Pitx2/RIEG result in laterality‐associated cardiac anomalies. In animal models, a common read‐out after the misexpression of laterality genes is heart looping direction. Missing in these studies is how laterality genes impact on downstream morphogenetic processes to coordinate heart looping. Previously, we showed that Pitx2 indirectly regulates flectin protein by regulating the timing of flectin expression in one heart field versus the other (Linask et al. [2002] Dev. Biol. 246:407–417). To address this question further we used a reported loss‐of‐function approach to interfere with chick CFC expression (Schlange et al. [2001] Dev. Biol. 234:376–389) and assaying for flectin expression during looping. Antisense CFC treatment results in abnormal heart looping or no looping. Our results show that regardless of the sidedness of downstream Pitx2 expression, it is the sidedness of predominant flectin protein expression in the extracellular matrix of the dorsal mesocardial folds and splanchnic mesoderm apposed to the foregut wall that is associated directly with looping direction. Thus, Pitx2 can be experimentally uncoupled from heart looping. The flectin asymmetry continues to be maintained in the secondary heart field during looping. Developmental Dynamics 228:217–230, 2003. © 2003 Wiley‐Liss, Inc.
Zwei neue fossile Hölzer der Morphogattung GinkgoxylonSaporta emend. Süss aus tertiären Schichten der Insel Lesbos, Griechenland, mit einer Übersicht über Fossilien mit ginkgoaler Holzstruktur
Authors: Süss H. 
Published: September 2003

AbstractDie Geschichte der Morphogattung Ginkgoxylon Saporta wird diskutiert, ihre Diagnose verändert und aus dem Versteinerten Wald von Lesbos, Griechenland, werden zwei neue untermiozäne Ginkgoxyla als Ginkgoxylon lesboense sp. nova und G. diversicellulatum sp. nova beschrieben. In einer Übersicht sind die bisher bekannten Fossilien mit ginkgoaler Holzstruktur zusammengestellt. Außerdem werden die Ursachen, die zu schiefgestellten Holzstrahlen führen, diskutiert.
What is Sium frigidumHand.‐Mazz. (Umbelliferae)?
Authors: Pimenov M. G. , Kljuykov E. V. 
Published: September 2003

AbstractA rare and enigmatic Chinese species, known as Apium ventricosum H. Boissieu and Sium frigidum Hand.‐Mazz. (the latter name is only used in current floristic literature), has been shown to be closer related to Sinocarum H. Wolff ex Shan RenHwa & Pu FaTing. This affinity, indicated recently by ITS sequence investigation, was confirmed by morphological analysis. Attribution of the species to Apium, Sium, or Chamaesium, was not confirmed by molecular and morphological data either. A new combination, Sinocarum ventricosum (H. Boissieu) Pimenov & Kljuykov, has been proposed. The isolated position of S. ventricosum within the genus Sinocarum is emphazised by separation of a new monotypic section, Sinocarum sect. Apiopsis Pimenov & Kljuykov.
Contribution to the knowledge of the Flora of the Mongolian Altai
Authors: Neuffer B. , Oyuntsetseg B. , Schamsran Z. , Friesen N. , Hurka H. 
Published: September 2003

AbstractDuring a German‐Mongolian expedition to the Mongolian Altai in July/August 2000, 404 specimens of vascular plants were collected. They are deposited in the Herbarium of the University of Osnabrück (OSBU). 381 specimens could be determined conclusively. The collected material comprises 300 species, 156 genera, and 44 families. Six of these species were first records for Mongolia, six species had not been recorded so far for the region Mongolian Altai, five are new for the region Khobdo, and 19 species new records for both regions, Mongolian Altai and Khobdo, Western Mongolia. A list of the collected plants with accession numbers and provenances is presented.
Estradiol increases extracellular levels of vascular endothelial growth factor in vivo in murine mammary cancer
Authors: Dabrosin Charlotta , Margetts Peter J. , Gauldie Jack 
Published: September 2003

AbstractAngiogenesis is essential for tumor growth and metastasis and an important prognostic factor in breast cancer. VEGF, a key factor for angiogenesis, has been correlated with tumor vessel density in breast cancer. Estrogen, another crucial factor in breast cancer, stimulates VEGF; and an ERE in the VEGF gene has been defined. VEGF is bioactive in the extracellular fluid, where it becomes available to endothelial cells. Whether E2 affects VEGF levels in the extracellular fluid is not known. We show, using intratumoral microdialysis in vivo, that E2 treatment increased tumor extracellular levels of VEGF in an estrogen‐dependent breast cancer model. Moreover, extracellular levels of VEGF in the tumor showed a strong correlation with total tumor VEGF, contrary to plasma levels of VEGF. Ninety‐three percent of measured VEGF in the extracellular fluid in the tumor was tumor‐derived, while only 45% of VEGF in circulating plasma originated from the tumor. We conclude that E2 increases extracellular VEGF and that microdialysis is a sensitive method for measurement of local VEGF production in vivo. Our results have potential application to the assessment of tumor characteristics in vivo in human tumors for individualized cancer therapy. © 2003 Wiley‐Liss, Inc.
Cytokeratin 20 and guanylyl cyclase C mRNA is largely present in lymph node and liver specimens of colorectal cancer patients
Authors: Conzelmann Michael , Dieterle Christoph P. , Linnemann Ulrich , Berger Martin R. 
Published: September 2003

AbstractThe aim of our prospective study was to detect circulating epithelial cells (CEC) indicating the presence of disseminated tumor cells (DTC) in tissues affected by lymphatic and hematogenic colorectal cancer metastasis. DTC were tracked in lymph node, liver or bone marrow samples of 245 colorectal cancer patients using 2 independent RT‐PCR assays for cytokeratin 20 (CK20) and guanylylcyclase C (GCC) that demonstrated a sensitivity of 1 colorectal cancer cell in 106 nucleated hematopoietic cells. CK20 mRNA was detected in 79% of lymph nodes, 35% of both liver lobes and 11% of bone marrow samples. GCC mRNA was found in 68% of lymph nodes, 60% of both liver lobes and 6% of bone marrow specimens. Both markers were recorded in 63% of lymph nodes, 45% of at least 1 liver lobe and 1% of bone marrow samples. There was no significant difference when comparing lymph node samples tested positive for both markers in patients with (N1/2; 65%) and without (N0; 56%) nodal involvement. The same was true when comparing the percentages of patients with and without clinically overt distant metastasis who were positive for both markers in at least 1 liver lobe (62% vs. 41%) or in bone marrow (4% vs. 0%). A score denoting the cumulative sum of tests indicating presence of CK20 and GCC mRNA in the liver was significantly related with UICC classification (p = 0.039). However, addition of lymph node results to this score decreased the correlation. The high incidence of clinically inconspicuous lymph node and liver samples tested positive for both markers emphasizes the function of these organs as primary filters for epithelial cells possibly shed from colorectal carcinomas. The potential prognostic significance of these findings warrants verification, especially regarding the importance of CEC or DTC resident in the liver of colorectal cancer patients. © 2003 Wiley‐Liss, Inc.