All animal (Mus musculus) experiments were carried out in accordance with the United Kingdom Animal Scientific Procedures Act (1986) and UK Home Office regulations under project license numbers 70/7926 and PDCC6E810. Skeletal preparations were performed as previously described (Rigueur and Lyons, 2014). Thus, YAP/TAZ activity controls chondrocyte proliferation in vitro, possibly reflecting a regenerative response, but is dispensable for chondrocyte proliferation in vivo, and instead functions to control cartilage morphogenesis via regulation of the extracellular matrix. Es zeigt sich ein starkes Nord-Süd-Gefälle, und viele Elite-Unis wie Harvard sind ganz streng  Thomas Winkler, Das Buch „Den Betroffenen eine Stimme geben“ handelt von Opfern der DDR-Heimerziehung. The effect of genotype on percentage Alcian Blue-stained area was significant (P=0.0138). Asterisks in G indicate specific bend regions in the spine that are not present in the spine of the control. In contrast, there was an expansion of the round proliferating zone and the pre-hypertrophic/hypertrophic zone in the Yapfl/flTazfl/flCol2a1cre+ve growth plates compared with control, suggesting defects in these stages of chondrogenesis (Fig. 4A,B). We note that phenotyping at E17.5 does not discern the direct early effects of YAP/TAZ deletion and that, to address this issue, earlier stages of development would need to be examined. Meckel's cartilage in the mutants (right panels) was shorter with abnormal morphology (white arrow), including an additional partial rotation at the posterior (arrowhead) before the malleus (M) and incus (I). The band mostly plays songs it writes and arranges itself. Given that chondrocytes secrete large amounts of specialised collagen II- and aggrecan-based ECM material to produce cartilage, it is plausible that the Hippo pathway functions to sense and regulate ECM synthesis and/or remodelling. n=4 control (Col2a1cre−ve) and n=4 Yapfl/flTazfl/flCol2a1cre+ve tibial growth plates. The Hippo signaling pathway has been implicated in tumor growth, sparking interest in the pathway as a potential therapeutic target. Conceptualization: H.K.V., B.T. Positional information was then binned in Prism 8. Data were analysed by t-tests comparing each mutant with control and adjusted for multiple testing with a 5% false discovery rate. Rainn Wilson 9. Ex vivo CT scans were acquired using a SkyScan 1176 CT scanner (Bruker MicroCT) with the source voltage set to 50 kV, the source current set to 500 µA, a frame averaging of 5, and a 0.5° step size over a 360° trajectory. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. Join our mailing list to receive news and updates on the series. Schrumpfen im Inland, Wachstum im Ausland: Die NBA startet mehr denn je als globale Marke in die neue Basketballsaison. (R) Frontal cut-away of HREM three-dimensional renderings of control (Col2a1cre−ve) and Yapfl/flTazfl/flCol2a1cre+ve foetuses at E14.5 along the anterior-posterior length of the palate. The effect of genotype on relative zone size was not significant (P=0.9823). The presence of the Col2a1cre+ve allele alone also did not affect total growth plate length or the size of individual zones (Fig. S4). Skeletal preparations of these animals revealed subtle skeletal malformations including spine deformities, a barrel-like ribcage and sternum and a loss of convex shape of the nasal bone (Fig. 2B,C,G,H). Primers are listed in Table S1. Fresh-frozen cryosections (anti-YAP) were fixed in 4% paraformaldehyde for 10 min direct from storage then washed in PBS. Here, we examined the consequence of disruption of mechanical signaling on soluble signaling pathways. Thomas Winkler, Alle Rechte vorbehalten. Data were analysed by multiple t-tests and corrected for multiple testing (I; # indicates adjusted P<0.01) or unpaired t-test (J; P=0.252). HREM data derived from n=5 control, n=3 non-cleft mutant, n=4 elevated and n=4 non-elevated cleft palate mutants. Dem deutschamerikanischen Footballer Amon-Ra St. Brown glückt ein seltenes Kunststück. (L,M) Quantification of the length of the growth plate (L) and length of each growth plate zone relative to the total length of the growth plate (M) in n=3 control (Col2a1cre−ve) and n=4 nls-YAP5SAKI/+Col2a1cre+ve E17.5 pups. White arrow indicates hunch in neck and white arrowhead indicates flattened morphology of the snout. Die New York Jets sind die Lachnummer der NFL. The defects observed here in Yapfl/flTazfl/flCol2a1cre+ve mutant animals closely phenocopy the defects described in Ctgf knockout animals, including malformed Meckel's cartilage and cleft palate (Ivkovic et al., 2003). Published by The Company of Biologists Ltd. MMP16 is a membrane-tethered MMP capable of degrading type II collagen, and dual deletion of Mmp16 and the closely related Mmp14 in mice results in increased ECM accumulation in the femoral growth plate (Shi et al., 2008). At E18.5, compared with Col2a1cre−ve control littermates, Lats1/2fl/flCol2a1cre+ve pups once again had extremely severe chondrodysplasia that was highly similar to and more severe than that of nls-YAP5SAKI/+Col2a1cre+ve mutants (Fig. 6A-J). The two known direct targets of YAP/TAZ, Ctgf and Cyr61, have well-documented roles in cartilage development (O'Brien and Lau, 1992; Wong et al., 1997). Here, we show that the Hippo pathway effectors YAP and TAZ work as crucial sign … For timed matings, E0.5 was designated as midday following the morning of finding the vaginal plug. This tumour suppressor pathway consists of a core kinase cascade in which the upstream kinase MST1/2 (Hippo in Drosophila) phosphorylates the downstream kinase LATS1/2 (Warts in Drosophila), which in turn phosphorylates and inactivates the pro-proliferative transcriptional co-activators YAP (Yes-associated protein, also known as YAP1) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1), which act via TEAD-family DNA-binding transcription factors to control gene expression in response to a variety of upstream inputs (Harvey and Tapon, 2007; Moya and Halder, 2019; Pan, 2007; Yu et al., 2015; Zheng and Pan, 2019). Interestingly, matrix metalloprotease enzymes are downstream target genes of YAP that can be induced upon integrin binding to stiff matrix substrates (Chakraborty et al., 2017; Nukuda et al., 2015) or dense matrix (Stanton et al., 2019). Thus, our findings refine the current model, namely that YAP and TAZ control cartilage development exclusively via direct regulation of Sox9, and support the notion that regulation of cartilage morphogenesis, particularly by remodelling the ECM through regulation of Ctgf, Cyr61 and various ECM proteases, is a primary physiological function for Hippo-YAP/TAZ signalling in this tissue. To examine the molecular consequence of YAP hyperactivation, we performed RTqPCR analysis on microdissected tibial sections from control (Col2a1cre−ve) and YAP5SAKI/+Col2a1cre+ve E17.5 samples. Black arrow indicates abnormal morphology of the c1 (atlas) vertebra and black arrowheads indicate the flattened rostrum of the skull and the barrel-like ribcage and curved sternum in the Yapfl/flTazfl/flCol2a1cre+ve mutant compared with control. Percentage thresholded area was then measured. The models were fitted in R using the function lmer of the R package lme4 (Bates et al., 2015). Primary antibodies were diluted in 1% bovine serum albumin (BSA) in PBS at 1:250 for anti-SOX9 (AB5535, Sigma-Aldrich), 1:50 for anti-COLXaI (14-9771-82, Invitrogen) and 1:100 for anti-YAP (14074, Cell Signaling Technology). ; Methodology: H.K.V., F.P., S.B., A.H., R.E.S., T.S., M.H., T.J.M., B.T. The resulting phenotypes are stronger than those previously reported and allow us to clarify the existing models of Hippo pathway function in cartilage. RTqPCR was performed on the QuantSudio 7 Flex PCR System (Applied Biosystems) using PowerUp SYBR Green Master Mix (Thermo Fisher Scientific). Haematoxylin and Eosin (H&E) staining of sections of E17.5 control (Col2a1cre−ve), single mutants (Yapfl/flTaz+/+Col2a1cre+ve, Yap+/+Tazfl/flCol2a1cre+ve), animals retaining one intact copy of either Yap or Taz (Yapfl/+Tazfl/flCol2a1cre+ve and Yapfl/flTaz+/flCol2a1cre+ve, respectively) and the double mutant (Yapfl/flTazfl/flCol2a1cre+ve) revealed that only the growth plate of the double mutant was changed in total length (Fig. 4A) and length of each growth plate zone (Fig. 4B) compared with the control. Primary chondrocytes from the ribs and sterna were isolated essentially as described previously (Mirando, 2014). Whole E17.5 pups were fixed in 10% neutral buffered formalin for two days then transferred to 70% ethanol. RNA was extracted using the Trizol manufacturer's instructions. "— Taz "With Hooligan, Philipp Winkler has shot a flare right in the middle of the other side's block of fans. Muppala S, Raghunathan VK, Jalilian I, Thomasy S , Murphy CJ. The Yapfl and Tazfl (Wwtr1fl) (Gruber et al., 2016), nls-YAP5SAKI (Vincent-Mistiaen et al., 2018), Latsfl and Lats2fl (Yi et al., 2016), Col2a1cre (Ovchinnikov et al., 2000) and Col2a1cre-ERT (Nakamura et al., 2006) strains have all been previously described. 2019 03; 180:102-109. The basisphenoid cartilage of the cranial base was wider in all three classes of mutant palates compared with control, whilst the pterygoid processes angled towards the midline in controls and non-cleft mutants (Fig. 3K,L) but angled laterally in both classes of cleft mutants (Fig. 3M,N). At E14.5, the palatal shelves are positioned vertically above the tongue and continue to grow toward the midline where they meet and fuse by around E15.5. We confirmed increased Yap levels to almost twice that of control and no change in Taz expression (Fig. 7H). The Hippo signalling pathway was discovered as a potent regulator of organ size in Drosophila, and is conserved in mammals (Harvey and Tapon, 2007; Moya and Halder, 2019; Pan, 2007; Yu et al., 2015; Zheng and Pan, 2019). The effect of genotype on length was not significant (P=0.8110). Scale bars: 200 µm (A,K); 50 µm (C,F). Genossenschaft seit 1992. However, the density of cells per region counted was reduced in the mutants (Fig. 4E). Similarly, we found a decrease in body size when we expressed the nuclear-targeted YAP allele, nls-YAP5SA, in chondrocytes (nls-YAP5SAKI/+Col2a1cre+ve); however, this phenotype was substantially more severe than the previously reported phenotypes and was accompanied by catastrophic chondrodysplasia resembling achondrogenesis (Fig. 5A-F). Strikingly, we found that the pattern and levels of expression of SOX9 was essentially normal in Yapfl/flTazfl/flCol2a1cre+ve tibias and in nls-YAP5SAKI/+Col2a1cre+ve tibias relative to total growth plate size (Fig. S5A-D). After airdrying the slides at room temperature, sections were visualised in brightfield on the Laser Capture Microdissector (LMD7000, Leica) and a 300 µm-wide box drawn down the midline on the tibial growth plate. Technical Boy 2. Notably, apoptosis was unchanged in all genotypes (Fig. Compared with the lateral emergence of the ribs from the spine in controls, the ribs of Yapfl/flTazfl/flCol2a1cre+ve pups emerged slightly to the anterior before angling sharply down towards the posterior (Fig. 2C,H). Data were analysed and found to be significant by unpaired t-test (L) and two-way ANOVA with growth plate zone and genotype as the independent variables, relative zone size as the dependent variable (M). Micro CT scanning of the tibias revealed the presence of mineralised bone surrounding a persistent shaft of chondrocytes, albeit appearing non-uniform in its surface (Fig. 6L). The differentiation of chondrocytes and the remodelling of cartilage into mineralised bone requires the activity of numerous proteases, including matrix metalloproteases (MMPs) and Cathepsin K (CTSK) and a decrease in protease activity can reduce the turnover of ECM proteins. Contrary to the previous findings that YAP/TAZ represses Sox9 or induces Sox6 (Deng et al., 2016; Goto et al., 2018), we did not detect a substantial change in either Sox9 expression or Sox6 levels in the double knockout growth plates (Fig. 7B). Jack Gleeson 1. Deng et al. ... Philip Michael Thomas 1. This research was supported by the Francis Crick Institute (FC001180), the Wellcome Trust (FC001180), Medical Research Council (FC001180), Cancer Research UK (FC001180) and the Australian National University (R4210005). Endochondral skeletal development begins with formation of cartilage (chondrogenesis), the size and shape of which largely prefigures that of the resulting bony skeleton and, consequently, the size and shape of the entire body. The effect of genotype on proliferation (D) was not significant (P=0.0550) and effect of genotype on cell density (E) was significant (P=0.0186). To examine the consequence of complete loss of the YAP and TAZ co-activators on in vitro proliferation of primary chondrocytes, we crossed Yapfl/flTazfl/+Col2a1cre+ve with Yapfl/flTazfl/fl mice to produce litters containing Yapfl/flTazfl/flCol2a1cre+ve animals. Consistent with our findings, a recent study has suggested that YAP/TAZ mediates TGF-β-induction of bone matrix remodelling factors Ctsk, Mmp13 and Mmp14 (Kegelman et al., 2020). Scale bars: 150 µm (A,C). Teddy 3. (A-F) Ventral (A,B), dorsal (C,D) and lateral (E,F) views of control (Col2a1cre−ve) (A,C,E) and nls-YAP5SAKI/+Col2a1cre+ve (B,D,F) E17.5 pups. (B) Proliferation, measured by confluence (percentage cell coverage) of field of view, of cultures from A. CTGF has been shown to bind to ECM components including aggrecan (Aoyama et al., 2009) as well as to cell surface integrins (Nishida et al., 2007) and a range of growth factors. Note the curvature of the tibia in J compared with E. (K) Measurements of femurs and tibias from skeletal preparations of n=4 control (Col2a1cre−ve) and n=4 Yapfl/flTazfl/flCol2a1cre+ve pups. Thomas Winkler. Ted Mosby 1. Ja, ich will Gerade nicht. The palatal shelves (PS) of 5/6 controls were elevated and partially or completed fused. Although primary cultured chondrocytes in vitro responded to YAP/TAZ loss-of-function or YAP gain-of-function according to the canonical understanding of YAP/TAZ being positive regulators of cell proliferation, identical genetic alterations in vivo did not affect chondrocyte proliferation. All mice were maintained on a mixed, predominantly C57Bl/6J background. Philipp Winkler was born near Hanover, Germany, in 1986 and has spent time in Japan, Kosovo, Albania, and Serbia. CTSK cleaves the major cartilage ECM components collagen II and aggrecan (Hou et al., 2003; Kafienah et al., 1998), suggesting the increased area of ECM in double homozygous mutants may represent accumulated ECM proteins owing to decreased rate of degradation by CTSK, MMP2 and perhaps other ECM proteases. We found that YAP/TAZ are necessary and sufficient to drive chondrocyte proliferation in vitro, but are dispensable for chondrocyte proliferation in vivo. Of the ECM component genes examined, Col10a1 was significantly reduced (Fig. 7K) and though neither Mmp2 nor Ctsk showed a significant change in YAP5SAKI/+Col2a1cre+ve samples, there was a substantial increase in Mmp16 expression (Fig. 7L). Portia de Rossi 2. These results show that expression of a nuclear-targeted YAP protein in chondrocytes in vivo does not affect cell proliferation and instead causes severely abnormal cartilage morphogenesis and decreased size of skeletal elements, possibly via altering the ECM. Scale bars: 3 mm (A-J); 200 µm (K, upper); 170 µm (K, lower); 50 µm (N). All remaining statistical analyses were performed in Prism 8. Seit 2017 lebt die Musikerin Rasha Nahas in Berlin – für die Palästinenserin mit israelischem Pass ist das auch eine Identitätssuche. The phenotype of the nls-YAP5SA overexpression mutant reported here bears some resemblance to the published phenotype of Sox9fl/flCol2a1Cre+ve pups (Akiyama et al., 2002) and to animals with chondrocyte-specific expression of constitutively active β-catenin (Akiyama et al., 2004). ... Tara Thomas Body And Skin. To confirm the biological relevance of the nls-YAP5SAKI/+Col2a1cre+ve overexpression phenotype, we inactivated endogenous Hippo signalling through cartilage-specific conditional knockout of the upstream negative regulators of YAP, Lats1 and Lats2 (Lats1/2fl/flCol2a1cre+ve). (G-J) Lateral cut-away of HREM three-dimensional renderings of control (Col2a1cre−ve) (G) and Yapfl/flTazfl/flCol2a1cre+ve (H-J) E17.5 pups to reveal normal morphology of the cranial base (black arrow) with the tongue (T) sitting below the intact palate (white arrowhead) in the control (G) compared with the abnormally angled cranial base (black arrow, H-J) and the tongue adjacent to the cranial base in the mutants with cleft palate (I,J). Thomas Winkler. The scans were reconstructed using NRecon v1.7.3.0 software (Bruker MicroCT) with an 8.57 µm isotropic voxel size and analysed using Analyze v12.0 visualisation and analysis software (AnalyzeDirect). (C-F) Gross morphology of the ventral surface of the palate, with lower jaw removed, showing control palate (C) and Yapfl/flTazfl/flCol2a1cre+ve mutant palate (D-F), including an uncleft palate (D) or a narrow elevated (E) or wide unelevated (F) cleft palate. Interestingly, the defects in Meckel's cartilage can be overcome in Yapfl/flTazfl/flCol2a1cre+ve animals, resulting in normal mandibular morphology at E17.5 and even normal palate morphology in some mutants. To calculate percentage coverage by ECM, images were filtered in ImageJ with a Gaussian blur, then colours split and the red channel retained. (A,F) Lateral view of E17.5 control (Col2a1cre−ve) and Yapfl/flTazfl/flCol2a1cre+ve pups. In support of this notion, a recent study has demonstrated that YAP localisation and activity in the embryonic cartilaginous humerus is depended on mechanical stimulation derived from the surrounding muscle (Shea et al., 2020). We therefore scanned E17.5 animals using micro computed tomography (microCT) and measured the length of the mineralised component of the hind limb (Fig. 2L,M). To investigate the cellular basis for the YAP/TAZ loss-of-function phenotype in cartilage, we focused on the growth plate of the proximal tibia, a commonly examined cartilage structure for the study of chondrocyte proliferation and differentiation in vivo. Reclaim your web. Growth plate regions were isolated from the centre of each chondrocyte zone and threshold using default settings. Vascular endothelial growth factor (VEGF) is a major driver of blood vessel formation. The hypoxic, stiff, and pro-angiogenic tumor microenvironment induces angiogenesis, giving rise to an immature, proliferative, and permeable vasculature. Tara Taz. (B,G) Lateral view of skeletal preparations of E17.5 control (Col2a1cre−ve) and Yapfl/flTazfl/flCol2a1cre+ve pups with forelimbs removed. YAP and TAZ were proposed to inhibit differentiation/maturation via direct repression of Sox9, an important regulator of chondrocyte cell fate (Goto et al., 2018), a model that conflicts with the general function of YAP/TAZ as transcriptional activators. (K-N) Frontal cut-away view of the palate (P) at the level of the pterygoid process. identify YAP/TAZ as essential co-transcription factors in endothelial cells during developmental angiogenesis. Chaired by: Thomas Lecuit. For RNA in situ hybridisation, RNAscope 2.5 HD Manual Assay (ACDBio) was performed according to manufacturer's instructions, using RNAscope probes for Ctgf (314541, ACDBio) and Cyr61 (429001, ACDBio). Along with Skaos from Bavarian Krumbach, No Sports, The Braces from Jülich, El Bosso & die Ping-Pongs from Munster and The Busters from Wiesloch, Blechreiz was one of the pioneers of the German ska scene at the end of the 1980s and the beginning of the 1990s. The presence of the Col2a1cre+ve allele alone had no substantive effect on proliferation of postnatal day (P) 0 primary chondrocytes (Fig. S1A,B). Nicht einfach, aber oft eine Beziehung für's Leben, sagt sie. (S) Threshold-isolated Meckel's cartilage from HREM three-dimensional renderings, representative of n=4 control (Col2a1cre−ve) and n=4 Yapfl/flTazfl/flCol2a1cre+ve samples. Asterisk indicates cleft palate. We next confirmed the RTqPCR reduction in Ctgf and Cyr61 by in situ hybridisation and saw comparable reductions in signal (Fig. 7F,G). Skeletal preparations revealed extremely dysmorphic skeletal elements throughout the body, including highly dysplastic facial bones, ectopic bone elements alone the spine and abnormal rib cage and limbs (Fig. 5G-J). This encodes a human YAP protein in which the LATS-target serines are modified to alanines, rendering the YAP protein refractory to negative regulation and cytoplasmic retention by the LATS1/2 kinases (Vincent-Mistiaen et al., 2018). (L) Quantification of percentage area occupied by ECM (Alcian Blue-stained area) per boxed region from K. Data were analysed by two-way ANOVA, with growth plate zone and genotype as the independent variables, percentage area Alcian Blue-stained as the dependent variable. 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and epithelial cell proliferation during lung branching morphogenesis, Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver, Hippo pathway coactivators Yap and Taz are required to coordinate mammalian liver regeneration, The hippo pathway effector Yap controls patterning and differentiation of airway epithelial progenitors, Mechanosignalling via integrins directs fate decisions of pancreatic progenitors, Hippo signaling is required for Notch-dependent smooth muscle differentiation of neural crest, CellProfiler 3.0: Next-generation image processing for biology, Proliferation assays (BrdU and EdU) on skeletal tissue sections, Isolation and culture of murine primary chondrocytes, Embedding embryos for high-resolution episcopic microscopy (HREM), YAP partially reprograms chromatin accessibility to directly induce adult cardiogenesis in vivo, Hippo-YAP/TAZ signalling in organ regeneration and regenerative medicine, Kinetics of tamoxifen-regulated Cre activity in mice using a cartilage-specific CreER(T) to assay temporal activity windows along the proximodistal limb skeleton, YAP regulates cell mechanics by controlling focal adhesion assembly, YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development, CCN2 (Connective Tissue Growth Factor) is essential for extracellular matrix production and integrin signaling in chondrocytes, The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass, Stiff substrates increase YAP-signaling-mediated matrix metalloproteinase-7 expression, Expression of the growth factor-inducible immediate early gene cyr61 correlates with chondrogenesis during mouse embryonic development, Col2a1-directed expression of Cre recombinase in differentiating chondrocytes in transgenic mice, Yap- and Cdc42-dependent nephrogenesis and morphogenesis during mouse kidney development, Yap and Taz are required for Ret-dependent urinary tract morphogenesis, A critical role for NF2 and the Hippo pathway in branching morphogenesis, Altered mandibular development precedes the time of palate closure in mice homozygous for disproportionate micromelia: an oral clefting model supporting the Pierre-Robin sequence, YAP inhibition enhances the differentiation of functional stem cell-derived insulin-producing beta cells, β1 integrin-dependent Rac/group I PAK signaling mediates YAP activation of Yes-associated protein 1 (YAP1) via NF2/merlin, Yap1 acts downstream of alpha-catenin to control epidermal proliferation, Localization of YAP activity in developing skeletal rudiments is responsive to mechanical stimulation, Membrane-type MMPs enable extracellular matrix permissiveness and mesenchymal cell proliferation during embryogenesis, Src Inhibits the Hippo Tumor Suppressor Pathway through Tyrosine Phosphorylation of Lats1, Biochemical ligand density regulates yes-associated protein translocation in stem cells through cytoskeletal tension and integrins, Altered endochondral bone development in matrix metalloproteinase 13-deficient mice, Skeletal dysplasias in the newborn: diagnostic evaluation and developmental genetics, Crumbs3-mediated polarity directs airway epithelial cell fate through the Hippo pathway effector Yap, MT1-MMP-dependent control of skeletal stem cell commitment via a beta1-integrin/YAP/TAZ signaling axis, Cartilage-specific over-expression of CCN family member 2/connective tissue growth factor (CCN2/CTGF) stimulates insulin-like growth factor expression and bone growth, YAP drives cutaneous squamous cell carcinoma formation and progression, MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes, Yap and Taz play a crucial role in neural crest-derived craniofacial development, Integrin-YAP/TAZ-JNK cascade mediates atheroprotective effect of unidirectional shear flow, YAP/TAZ orchestrate VEGF signaling during developmental angiogenesis, Visualising the cardiovascular system of embryos of biomedical model organisms with high resolution episcopic microscopy (HREM), Heterozygous loss-of-function mutations in YAP1 cause both isolated and syndromic optic fissure closure defects, Cyr61, product of a growth factor-inducible immediate-early gene, regulates chondrogenesis in mouse limb bud mesenchymal cells, Integrin α2β1 inhibits MST1 kinase phosphorylation and activates Yes-associated protein oncogenic signaling in hepatocellular carcinoma, Hippo pathway effector Yap promotes cardiac regeneration, Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation, YAP and ERK mediated mechanical strain-induced cell cycle progression through RhoA and cytoskeletal dynamics in rat growth plate chondrocytes, YAP1 negatively regulates chondrocyte differentiation partly by activating the β-catenin signaling pathway, Large tumor suppressor homologs 1 and 2 regulate 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inhibition of Yes-associated protein (Yap) overabundance, Chondrocytes transdifferentiate into osteoblasts in endochondral bone during development, postnatal growth and fracture healing in mice, Capillarity and active cell movement at mesendoderm translocation in the Xenopus gastrula, MFN2 interacts with Nuage-associated proteins and is essential for male germ cell development by controlling mRNA fate during spermatogenesis, The intrinsically disordered protein SPE-18 promotes localized assembly of MSP in, https://dev.biologists.org/lookup/doi/10.1242/dev.187187.supplemental, http://creativecommons.org/licenses/by/4.0, https://creativecommons.org/licenses/by/4.0, https://dev.biologists.org/lookup/doi/10.1242/dev.187187.reviewer-comments.pdf, A new society for regenerative biologists, International Society for Regenerative Biology, The Immune System in Development and Regeneration, Institutional usage stats (logged-in users only), © 2020.
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