6,571 research outputs found
Willin, an upstream component of the Hippo signaling pathway, orchestrates mammalian peripheral nerve fibroblasts
No full textWillin/FRMD6 was first identified in the rat sciatic nerve, which is composed of neurons, Schwann cells, and fibroblasts. Willin is an upstream component of the Hippo signaling pathway, which results in the inactivation of the transcriptional coactivator YAP through Ser127 phosphorylation. This in turn suppresses the expression of genes involved in cell growth, proliferation and cancer development ensuring the control of organ size, cell contact inhibition and apoptosis. Here we show that in the mammalian sciatic nerve, Willin is predominantly expressed in fibroblasts and that Willin expression activates the Hippo signaling cascade and induces YAP translocation from the nucleus to the cytoplasm. In addition within these cells, although it inhibits cellular proliferation, Willin expression induces a quicker directional migration towards scratch closure and an increased expression of factors linked to nerve regeneration. These results show that Willin modulates sciatic nerve fibroblast activity indicating that Willin may have a potential role in the regeneration of the peripheral nervous system.Peer reviewe
MM210 Yap magnetometer 1 min resolution data distributed by ERG-SC
No full textGeomagnetic field data with 1 min resolution for Yap of 210 Magnetic Meridian (210MM) magnetometer network, distributed as CDF files by ERG-SCdatase
A reciprocal regulatory loop between TAZ/YAP and G-protein Gαs regulates Schwann cell proliferation and myelination
No full textAbstractSchwann cell (SC) myelination in the peripheral nervous system is essential for motor function, and uncontrolled SC proliferation occurs in cancer. Here, we show that a dual role for Hippo effectors TAZ and YAP in SC proliferation and myelination through modulating G-protein expression and interacting with SOX10, respectively. Developmentally regulated mutagenesis indicates that TAZ/YAP are critical for SC proliferation and differentiation in a stage-dependent manner. Genome-wide occupancy mapping and transcriptome profiling reveal that nuclear TAZ/YAP promote SC proliferation by activating cell cycle regulators, while targeting critical differentiation regulators in cooperation with SOX10 for myelination. We further identify that TAZ targets and represses Gnas, encoding Gαs-protein, which opposes TAZ/YAP activities to decelerate proliferation. Gnas deletion expands SC precursor pools and blocks peripheral myelination. Thus, the Hippo/TAZ/YAP and Gαs-protein feedback circuit functions as a fulcrum balancing SC proliferation and differentiation, providing insights into molecular programming of SC lineage progression and homeostasis.</jats:p
YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate
No full textAbstractHow the behaviour of somatic stem cells (SCs) is influenced by mechanical signals remains a black-box in cell biology. Here we show that YAP/TAZ regulation by cell shape and rigidity of the extracellular matrix (ECM) dictates a pivotal SC decision: to remain undifferentiated and grow, or to activate a terminal differentiation programme. Notably, mechano-activation of YAP/TAZ promotes epidermal stemness by inhibition of Notch signalling, a key factor for epidermal differentiation. Conversely, YAP/TAZ inhibition by low mechanical forces induces Notch signalling and loss of SC traits. As such, mechano-dependent regulation of YAP/TAZ reflects into mechano-dependent regulation of Notch signalling. Mechanistically, at least in part, this is mediated by YAP/TAZ binding to distant enhancers activating the expression of Delta-like ligands, serving as ‘in cis’ inhibitors of Notch. Thus YAP/TAZ mechanotransduction integrates with cell–cell communication pathways for fine-grained orchestration of SC decisions.</jats:p
SC author and illustrator Kate Salley Palmer signing book
No full textPhotograph of SC author and illustrator Kate Salley Palmer signing boo
Book signing by SC author and illustrator Kate Salley Palmer
No full textPhotograph of Book signing by SC author and illustrator Kate Salley Palme
Mioscarta translucida Crispolon & Yap 2021, sp. nov.
No full textMioscarta translucida Crispolon & Yap sp. nov. urn:lsid:zoobank.org:act: 7D16117A-699D-4C7E-B037-E290B274EA8C Fig. 11 Diagnosis M. translucida is the only species with tegmen translucid without any other coloration. Etymology The species name refers to the translucid tegmen and is based on the latin word “translucidus” which means allowing light to pass through. Material examined Holotype PHILIPPINES • ♂; “ Philippines, Camarines Sur, Luzon isl. Mt Isarog Natural Park, Panicuason Naga ”, “Muséum Paris; 1 May 2011; S.A. Yap, M.V. Yngente & O.L. Eusebio rec.”; “Muséum Paris, MNHN (EH) 24749 ”; MNHN. Description BODY. Length 10 mm (tegmina included), width 4 mm. HEAD (Figs 1A, 11B). In dorsal view, large ocelli, distance between eyes less than 8 times ocellus diameter, distance between ocelli equals one ocellus diameter, distance between ocellus and the compound eye 2 times ocellus diameter, ocelli closer to each other than from compound eyes. Eyes not prominent, length 1.44 times than wide. Vertex and frons longitudinal median carina absent. Vertex as long as wide with 3 times ocellus diameter in between two vertex grooves outside ocelli and 3 times ocellus diameter between anterior and posterior vertex margins. Postclypeus with longitudinal furrow, slightly swollen and ovoid shape in frontal view, widest part at mid height (Figs 1A, 11B), not receding and prior to anteclypeus where it bends forming right angle in lateral view (Fig. 11A). Rostrum long, surpassing mesocoxae. Thorax (Figs 2A, 11 A-C). In dorsal view, pronotum with anterior concavities on each side, anterior margin as wide as posterior margin of head including eyes, anterolateral margins curved, posterior margin grooved, postero-lateral margins slightly concave, longer than anterolateral margins, humeral angle rounded. In lateral view, pronotum curving not more than 25º (Figs 2, 11A) Scutellum as long as wide with large median dimple (Fig. 11C). Tegmen (Fig. 11A–C). R bifurcates on apical half, M bifurcate on basal third, apical reticulation not well developed without concave apical cells. Posterior wing (Fig. 3A). Rp separating from SC+Ra nearly at midlength, M reaches ambient vein, Cua and Cup fused at base and m-cu links M to Cua before Cua bifurcation, common base for Cup and Cua originate at base of wing, 7 longitudinal veins and 5 apical cells between SC+Ra and Cup, angular protrusion of costal margin near its base. Metafemur with apical spine in inner margin, metatibiae bearing 1 lateral spine. MALE TERMINALIA. In lateral view, posterior margin of pygofer slightly undulating in the middle with slight curved on the last third (Fig. 11E). Subgenital plates (Fig. 11F) dorsal and ventral margin of main plate roughly straight, sterno-lateral plate present, slightly elongated, intermediate plate present, elongated slightly triangular shaped, linking internal sides of lateral and subgenital plates. Paramere (Fig. 11G) not globose, dorsal margin convex and regularly curving finishing with rounded apex with very minute groove, ventral margin convex, apex with spiniform process pointing antero-ventrally. Dorsal and ventral margins of aedeagus undulating. Aedeagus (Fig. 11H) with basal third of dorsal margin regularly bent without angle before the bent part and last 2 ⁄ 3 vertical and S-shaped, ventral margin regularly curved then slightly concaved before the base, apical extension sharp pointing postero-ventrally, posterior protrusion sharp at the apex hook-shaped, postero-dorsal protrusion absent. COLOR. Head and pronotum brown with yellow patches, rostrum yellowish white, pedicel of antenna brown, legs yellowish and abdomen light brown. Tegmen partially translucid, opaque parts being yellowish with darker patches. Type Locality Philippines: Luzon, Camarines Sur, Mount Isarog Natural Park. Distribution Philippines: Luzon Island. Remarks The exact length of subgenital plate relative to height of pygofer is not provided because part of the appendage is damaged.Published as part of Crispolon, Elorde Jr. S., Guilbert, Eric, Yap, Sheryl A. & Soulier-Perkins, Adeline, 2021, New genus and new species of spittlebugs (Hemiptera: Cercopidae) from the Philippines, pp. 90-135 in European Journal of Taxonomy 778 on pages 113-116, DOI: 10.5852/ejt.2021.778.1571, http://zenodo.org/record/570497
Merlin controls the repair capacity of Schwann cells after injury by regulating Hippo/YAP activity
No full textLoss of the Merlin tumor suppressor and activation of the Hippo signaling pathway play major roles in the control of cellproliferation and tumorigenesis. We have identified completely novel roles for Merlin and the Hippo pathway effectorYes-associated protein (YAP) in the control of Schwann cell (SC) plasticity and peripheral nerve repair after injury. Injuryto the peripheral nervous system (PNS) causes a dramatic shift in SC molecular phenotype and the generation of repaircompetent SCs, which direct functional repair. We find that loss of Merlin in these cells causes a catastrophic failure ofaxonal regeneration and remyelination in the PNS. This effect is mediated by activation of YAP expression inMerlin-null SCs, and loss of YAP restores axonal regrowth and functional repair. This work identifies new mechanismsthat control the regenerative potential of SCs and gives new insight into understanding the correct control of functionalnerve repair in the PNS
Expanding the Hippo pathway : hMOB3 modulates apoptotic MST1 signaling and supports tumor growth in glioblastoma
No full textProtein kinases are critical players of signal transduction pathways involved in development, physiological and pathological processes. Deregulation of protein kinase signaling is found to be causal or related to varieties of human diseases, such as cancer, cardiovascular disease and diabetes. The human genome encodes 518 protein kinases. Approximately 60 out of them belong to the AGC group of Serine/Threonine protein kinases, including the ste20 like MST kinase family and NDR kinase family. Members of these families are highly conserved from yeast to men and regulate essential processes such as growth, proliferation and apoptosis. The Hippo pathway is a recently identified tumor suppressive network, where the MST-NDR family kinases form a kinase cascade regulating the downstream signaling through the effector YAP/TAZ.
In addition to signaling through the NDR family kinases, the Hippo/MST kinases also control cell apoptosis bypass these classical effectors YAP/TAZ. Despite the fact that JNK, FOXO3, H2B are well characterized downstream targets of apoptotic MST kinases, the regulatory mechanisms of apoptotic MST signaling are still largely unknown.
The human MOB family consists of six members encoded by six different genes (hMOB1A, -1B, -2, -3A, -3B and -3C). While as an activator for hMOB1A/B in MST-LATS/NDR kinase cascade, hMOB2 is a specific negative regulator of NDR kinase by competing the binding of hMOB1 to NDR kinase. Although hMOB3 family members share higher amino acid identity with hMOB1 than hMOB2, hMOB3 proteins do not interact or (de)activate NDR family kinases. Hence, the functions of hMOB3A/B/C are completely undefined.
A previous microarray study performed in the lab indicated that hMOB3 family members were deregulated in glioblastoma. In the present study, we first investigated the pathological roles of human MOB3 proteins and found that hMOB3 is highly upregulated in glioblastoma. Moreover, mRNA expression levels of hMOB3 members correlate with survival, suggesting hMOB3 members as potential prognostic markers. We extended the biochemical analysis by looking for the interaction partners of hMOB3 and demonstrated that hMOB3 binds to MST1 and inhibits the apoptotic cleavage of MST1 kinase. We further verified that hMOB3 promotes tumorigenesis of gliobalstoma cells in vivo by a U87MG derived flank model. Taken together, our results suggest that manipulate hMOB3 might represent a therapeutic strategy in malignant gliomas
Youth Access to Psychiatry Program (YAP-P) Newsletter, May 2024
No full textThe Youth Access to Psychiatry Program (YAP-P) includes a provider-to-provider psychiatric consultation line and behavioral health resource available to pediatric primary care providers through the SC Department of Mental Health. This electronic newsletter contains pertinent information related to the program
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