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PID2020-116806GB-I00

Financiado

LA B-CATENINA CONTROLA LA ADHESION Y LA DIFERENCIACION DE LAS CELULAS MADRE NEUR...

LA B-CATENINA CONTROLA LA ADHESION Y LA DIFERENCIACION DE LAS CELULAS MADRE NEURALES EMBRIONARIAS. IN THE EMBRYONIC NEURAL TUBE, NEURAL STEM CELLS (NSCS) FORM A PSEUDOSTRATIFIED, SINGLE-CELL LAYERED EPITHELIUM, EXTENDING FROM THE VENTRICLE TO THE BASAL LAMINA AND DISPLAYING MARKED APICO-BASAL POLARITY, THE PROTEINS PRESENT AT T... ver más

01/01/2020

CSIC

182K€

Presupuesto del proyecto: 182K€

Líder del proyecto

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGA... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 2-3 | 552M€

Financiación concedida El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2020-01-01 No tenemos la información de la convocatoria

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CSIC

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Líder del proyecto

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGA... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 2-3 | 552M€

Presupuesto del proyecto 182K€

Descripción del proyecto IN THE EMBRYONIC NEURAL TUBE, NEURAL STEM CELLS (NSCS) FORM A PSEUDOSTRATIFIED, SINGLE-CELL LAYERED EPITHELIUM, EXTENDING FROM THE VENTRICLE TO THE BASAL LAMINA AND DISPLAYING MARKED APICO-BASAL POLARITY, THE PROTEINS PRESENT AT THE APICAL POLE OF NSCS ARE COLLECTIVELY CALLED THE APICAL COMPLEX (AC), FORMING THREE CONCENTRIC SUB-DOMAINS; N-CADHERIN, α-CATENIN AND B-CATENIN ARE LOCATED IN THE SUB-APICAL DOMAIN FORMING THE JUNCTIONAL COMPLEXES, DURING DEVELOPMENT, NSCS CAN INITIALLY BE IDENTIFIED BY THE EXPRESSION OF SOX2, AND THESE CELLS PROLIFERATE SYMMETRICALLY IN A SELF-EXPANDING MODE, LATER ON, AND IN ASSOCIATION WITH THE ONSET OF NEUROGENESIS, THEIR MODE OF DIVISION CHANGES TO GENERATE THE FIRST COMMITTED NEURONS IN THESE NEUROGENIC DIVISIONS, POST-MITOTIC NSCS DAMPEN THEIR EXPRESSION OF N-CADHERIN AND THEY DETACH FROM THE PROLIFERATIVE VENTRICLE, THUS, IT IS CRITICAL TO COORDINATE NSC DIFFERENTIATION AND DELAMINATION IN ORDER TO MAINTAIN THE ARCHITECTURE OF THE NERVOUS SYSTEM, B-CATENIN MEDIATES CANONICAL WNT SIGNALLING, STIMULATING TCF DEPENDENT TRANSCRIPTION, HOWEVER, β-CATENIN ALSO PLAYS IMPORTANT ROLES IN EPITHELIAL CELL POLARITY, FOR EXAMPLE ASSOCIATING WITH CLASSIC CADHERINS THROUGH ITS ARMADILLO DOMAINS AND THEREBY CONTRIBUTING TO ADHERENS JUNCTION (AJ) FORMATION,THE HYPOTHESIS OF THE PROJECT PROPOSES THAT DURING THE NERVOUS SYSTEM DEVELOPMENT B-CATENIN CARRIES OUT TWO SEQUENTIAL BUT INTERCONNECTED ACTIVITIES, DURING NSCS PROLIFERATION B-CATENIN ACTIVITY IS ESSENTIAL FOR THE FORMATION AND MAINTENANCE OF THE AJS AND SPECIALLY FOR N-CADHERIN RELATED ADHESION AND POLARITY, DURING THIS PERIOD B-CATENIN IS DOCKED AT THE AJS, PREVENTING THIS WAY UNDESIRED TRANSCRIPTIONAL ACTIVITY, WHEN NEUROGENESIS BEGINS, NEWLY SYNTHETIZED B-CATENIN IS REDIRECTED TOWARDS THE NUCLEUS WHERE IT ACTIVATES TCF DEPENDENT TRANSCRIPTION, IN CONTRAST TO THE STEMNESS PROMOTING EFFECTT DEVELOPED IN NSCS, DURING NEUROGENESIS B-CATENIN IS CRUCIAL FOR NEURAL DIFFERENTIATION,TO VALIDATE OR REFUTE THIS HYPOTHESIS WE PROPOSE TWO GENERAL OBJECTIVES:FIRST: WE NOW KNOW THAT B-CATENIN CONTRIBUTES TO AJS PROMOTING N-CADHERIN MATURATION, HOWEVER NEW RESULTS AS THE INTERACTION WITH VINCULIN AND ITS EFFECTS ON INM AND CELL CYCLE TOLD AS THAT THE REGULATION CARRIED OUT BY B-CATENIN IS EVEN MORE RELEVANT THAT WE FIRSTLY BELIEVED, THEREFORE, WE PROPOSE TO STUDY THE ROLE PLAYED BY THE DIFFERENT PROTEINS ASSOCIATED WITH THE N-CADHERIN/B-CATENIN COMPLEX ON THE FORMATION OF THE AC/AJS, HOW THEY REGULATE APICAL AND NUCLEAR POOLS OF B-CATENIN AND THE EFFECTS OF THEIR DEREGULATION ON THE POLARITY, PROLIFERATION AND DIFFERENTIATION OF NEUROBLASTS, DEVOTING SPECIAL INTEREST IN THE RELEVANCE OF THESE AC/AJS ASSOCIATED PROTEINS ON B-CATENIN DEPENDENT TUMOUR PROGRESSION,SECOND: WE FOUND THAT TCF DEPENDENT TRANSCRIPTION BECAME ACTIVATED DURING NEUROGENESIS QUITE LONG AGO, HOWEVER IT HAS BEEN RECENTLY THAT WE DEVELOPED ALL THE TOOLS THAT REALLY ALLOWED TO DISSECT ALL THE EVENTS OCCURRING DURING THIS PROCESS, THEREFORE, WE PROPOSE TO STUDY IN DETAIL THE TIME SEQUENCE AND THE MOLECULAR ELEMENTS INTERVENING IN SUCH PROCESS, MOREOVER, WE ALREADY KNOW WHAT HAPPENS IF AN ANOMALOUS TCF TRANSCRIPTIONAL ACTIVITY OCCURS DURING NSCS PROLIFERATION, BUT WE HAVE NO CLUE ABOUT WHAT IS THE RESULT IF IT HAPPENS WHEN NEUROGENESIS ALREADY STARTED, I MEAN WE WILL STUDY THE CONSEQUENCES OF THE FAILURE OF WHAT WE COULD CALL AS THE B-CATENIN SECOND LIFE, POLARIDAD CELULAR\UNION ADHERENTE\B-CATENINA\N-CADHERINA\ADHESION CELULAR\CELULAS MADRE NEURALES EMBRIONARIAS\MEDULOBLASTOMA\INVASION TISULAR\ONCOGEN\SUPRESOR DE TUMORES.

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