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<br>[1]. Tanaka et al (2005) FGF-induced vesicular release of sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination. Nature 435 172.
Abstract
The precise specification of left-right asymmetry is an essential process for patterning internal organs in vertebrates. In mouse embryonic development, the symmetry-breaking process in left-right determination is initiated by a leftward extraembryonic fluid flow on the surface of the ventral node. However, it is not known whether the signal transduction mechanism of this flow is chemical or mechanical. Here we show that fibroblast growth factor (FGF) signalling triggers secretion of membrane-sheathed objects 0.3-5?μm in diameter termed /’nodal vesicular parcels/’ (NVPs) that carry Sonic hedgehog and retinoic acid. These NVPs are transported leftward by the fluid flow and eventually fragment close to the left wall of the ventral node. The silencing effects of the FGF-receptor inhibitor SU5402 on NVP secretion and on a downstream rise in Ca2+ were sufficiently reversed by exogenous Sonic hedgehog peptide or retinoic acid, suggesting that FGF-triggered surface accumulation of cargo morphogens may be essential for launching NVPs. Thus, we propose that NVP flow is a new mode of extracellular transport that forms a left-right gradient of morphogens….
<br>[2]. Bojesen KB, Clausen O, Rohde K, Christensen C, Zhang L, Li S, Kohler L, Nielbo S, Nielsen J, Gjorlund MD, Poulsen FM, Bock E, Berezin V.Nectin-1 binds and signals through the fibroblast growth factor receptor.J Biol Chem. 2012 Sep 5.
Abstract
Nectins belong to a family of immunoglobulin(Ig)-like cell-adhesion molecules (CAMs) comprising four members, nectin-1 through nectin-4. Nectins are involved in formation of the mechanical adhesive puncta adherentia junctions (PAJs) of synapses. Nectins share the same overall structural topology with an extracellular region containing three Ig modules, a transmembrane region, and a cytoplasmic region. In nectin-1, the first and second Ig-module in the extracellular region is necessary for the trans-interaction with nectin-3 and formation of cis-dimers, respectively. The function of the third Ig-module of nectin-1 remains unknown. We here report the structure in solution of the third, membrane-proximal Ig module of mouse nectin-1 (nectin-1 Ig3) solved by means of nuclear magnetic resonance (NMR) spectroscopy. It belongs to the C1 set of the Ig superfamily. Nectin-1 Ig3 was produced as a recombinant protein and induced neurite outgrowth in primary cultures of hippocampal and cerebellar granule neurons (CGNs), an effect abolished by treatment with the fibroblast growth factor receptor (FGFR) inhibitor SU5402, or by transfection with a dominant-negative FGFR1 construct. We showed by surface plasmon resonance (SPR) analysis that nectin-1 Ig3 directly interacted with various isoforms of FGFR. Nectin-1 Ig3 induced phosphorylation of FGFR1c in the same manner as the whole nectin-1 ectodomain, and promoted survival of CGN induced to undergo apoptosis. Finally, we constructed a peptide, nectide, by employing in silico modeling of various FGFR ligand binding-sites. Nectide mimicked all the effects of nectin-1 Ig3. We suggest that FGFR is a downstream signaling partner of nectin-1.
<br>[3]. Zhu X, Li Z, Jiang D, Zhao J, Huang L, Zhang J, Huang X.Characterization and expressional analysis of Dleu7 during Xenopus tropicalis embryogenesis.Gene. 2012 Nov 1;509(1):77-84.
Abstract
We characterized the genomic structure and developmental expression of the Dleu7 (deleted in lymphocytic leukemia, 7) gene in Xenopus tropicalis and the evolution of the gene across species. Within the protein-coding sequence (CDS) region, X. tropicalis Dleu7 consists of two exons and one intron. However, bioinformatic analysis indicates that this 211-amino-acid protein contains no obvious functional domains or known motifs. Reverse-transcription polymerase chain reaction and whole-mount in situ hybridization results revealed that, in addition to its expression in the blood island region, some regions of the central nervous system, and subdomains of the neural tube, X. tropicalis Dleu7 is zygotically expressed primarily in mesoderm tissues such as notochord and muscles during early embryogenesis. Expression in notochord is consistent with results from genome-wide association studies suggesting that DLEU7 is related to human adult height. Expression in the blood island region, where blood cell precursors (including B cells) are generated, implies a potential conserved role for Dleu7 in B-cell development between amphibians and mammals. Expression of Dleu7 in some regions of the central nervous system and subdomains of the neural tube also suggests other functions in development. Phylogenetic analysis indicated that Dleu7 is a vertebrate-specific gene and undergoes strong selective pressure in lower vertebrates but is functionally constrained in higher mammals. When subcellular localization was examined by overexpression of enhanced green fluorescent protein fusion protein, Dleu7 showed centrosome localization with main distribution in cytoplasm. Treating gastrula embryos with SU5402, a small molecular inhibitor of the fibroblast growth factor (FGF) receptor, confirmed that Dleu7 expression in mesoderm is regulated by FGF signaling. Our data provide important clues for pathogenesis and physiology during development from the perspective of evolutionary conservation.
<br>[4]. Chen YH, Yu J.Ectopic expression of Fgf3 leads to aberrant lineage segregation in the mouse parthenote preimplantation embryos.Dev Dyn. 2012 Aug 28.
Abstract
Background: Parthenogenetic mammalian embryos were reported to die in utero no later than the 25-somite stage due to abnormal development of both embryonic and extraembryonic lineages. Interestingly, it has been shown that parthenogenetic ICM cells tend to differentiate more into primitive endoderm cells and less into epiblast and ES cells. Hence we are interested in studying the molecular mechanisms underlying lineage defects of parthenotes. Results: We found that parthenote inner cell masses (ICMs) contained decreased numbers of Sox2(+) /Nanog(+) epiblast cells but increased numbers of Gata4(+) primitive endoderm cells, indicating an unusual lineage segregation. We demonstrate for the first time that the increased Gata4 level in parthenotes may be explained by the strong up-regulation of Fgf3 and Fgfr2 phosphorylation. Inhibition of Fgfr2 activation by SU5402 in parthenotes restored normal Nanog and Gata4 levels without affecting Fgf3, indicating that Fgf3 is upstream of Fgfr2 activation. In parthenote trophectoderm, we detected normal Cdx2 but ectopic Gata4 expression and reduced Elf5 and Tbr2(Eomes) levels. Conclusions: Taken together, our work provides for the first time the insight into the molecular mechanisms of the developmental defects of parthenogenetic embryos in both the trophectoderm and ICM. Developmental Dynamics, 2012. ? 2012 Wiley Periodicals,Inc.
<br>[5]. Hirabayashi M, Tamura C, Sanbo M, Kato-Itoh M, Kobayashi T, Nakauchi H, Hochi S.A retrospective analysis of germline competence in rat embryonic stem cell lines.Transgenic Res. 2012 Aug 9.
Abstract
The factors responsible for conferring germline competence in embryonic stem (ES) cell lines remain unidentified. In the present study, rat ES cell lines (n = 17) were established with 3i medium (SU5402, PD0325901, CHIR99021), 2i medium (PD0325901, CHIR99021) or 2iF medium (PD0325901, CHIR99021, forskolin), and their potential for germline transmission to the G1 generation was examined. Rat strains were divided into an albino group (F344, Wistar or CAG/Venus transgenic rats with the Wistar background) or a colored coat group (Brown-Norway, Dark-Agouti, or BLK rats selected from >F3 generations of Wistar × Dark-Agouti rats based on their black coat color). Successful germline transmission was observed in 57 % (4/7), 40 % (2/5) and 100 % (5/5) of the ES cells established with 3i, 2i and 2iF media, respectively. ES cell lines from the homozygous CAG/Venus transgenic rats were established in all three media, but only the lines established with the 2iF medium were germline-competent. Neither coat-color (albino: 64 %, 7/11; colored: 67 %, 4/6) nor gender of the ES cell lines (XX: 67 %, 2/3; XY: 64 %, 9/14) were likely to affect germline transmission.
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