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(Created claim: summary (P836): BACKGROUND: CARDIAC DEVELOPMENT RESULTS FROM THE INTEGRATED ACTION OF INTERCELLULAR SIGNALS, EPIGENETIC AND TRANSCRIPTIONAL REGULATORS. THE COORDINATED ACTION OF THESE FACTORS REGULATES THE PROCESSES OF PROLIFERATION, PATTERN FORMATION AND CELL DIFFERENTIATION THAT ORIGINATE THE ADULT HEART, AND THEIR ALTERATION RESULTS IN CONGENITAL HEART DISEASE (CHD) THAT IMPACT ON NEONATAL OR ADULT LIFE. _x000D_ objectives: STUDY THE ROLE OF INTERCELLULAR S...) |
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BACKGROUND: CARDIAC DEVELOPMENT RESULTS FROM THE INTEGRATED ACTION OF INTERCELLULAR SIGNALS, EPIGENETIC AND TRANSCRIPTIONAL REGULATORS. THE COORDINATED ACTION OF THESE FACTORS REGULATES THE PROCESSES OF PROLIFERATION, PATTERN FORMATION AND CELL DIFFERENTIATION THAT ORIGINATE THE ADULT HEART, AND THEIR ALTERATION RESULTS IN CONGENITAL HEART DISEASE (CHD) THAT IMPACT ON NEONATAL OR ADULT LIFE. _x000D_ objectives: STUDY THE ROLE OF INTERCELLULAR SIGNALLING IN (1) THE DEVELOPMENT AND PATHOLOGY OF CARDIAC VENTRICLES AND CORONARY VASCULATURE, (2) DEVELOPMENT AND VALVE PATHOLOGY, AND (3) CARDIAC REGENERATION. _x000D_ hypotheses: IDENTIFYING THE MECHANISM OF ACTION OF SIGNALING PATHWAYS ESSENTIAL FOR CARDIAC DEVELOPMENT IS CRUCIAL FOR UNDERSTANDING ETIOLOGY AND DEVELOPING TREATMENTS FOR HDC. _x000D_ SPECIFIC objectives: CHARACTERISE: 1.1: MICE WITH MIB1 MUTATIONS CAUSING NON-COMPACTED MYOCARDIOPATHY (NCML). 1.2: CARDIAC DIFFERENTIATION OF HUMAN INDUCED PROGENITOR CELLS (HIPSC) MUTANT FOR MIB1. 1,3-1,5: THE FUNCTION OF GPR126 (1.3), SEMAFORINAS (1.4) AND NRG1 (1.5) IN CARDIAC DEVELOPMENT. 1.6: EPHRINB2 IN THE DEVELOPMENT OF CORONARY VASCULATURE. 2.1: NOTCH’S DEPENDENT SECRETOMA IN CARDIAC DEVELOPMENT. 2.2: GENES REGULATED BY NOTCH DURING CARDIAC DEVELOPMENT. 3.1: WNT’S ROLE IN THE VALVE DEVELOPMENT DEPENDENT ON JAG1/NOTCH1. 3.2: JAG1 AND JAG2 FUNCTION IN THE REMODELING OF THE OUTPUT TRACT (OFT) AND VALVE MORPHOGENESIS. 3.3: THE INVOLVEMENT OF NOTCH IN LVNC AND BAV (BICUSPIDE AORTICA VALVE). 4,1-4,2: FUNCTION OF MDK-A (4.1), CAV-1 AND CAVIN (4.2) IN THE CARDIAC REGENERATION OF THE ZEBRAFISH. _x000D_ Methodology: 1.1: ANALYSIS OF MICE CARRYING MIB1 V943F AND R530X MUTATIONS. 1.2: CARDIOMYOCYTIC DIFFERENTIATION OF HIPSC WITH MIB1 MUTATIONS. 1.3: CARDIAC PHENOTYPE OF MICE WITH FALTA- OR EXCESS-OF-FUNCTION OF ENDOCARDIAL GPR126. 1.4: GENERATION AND ANALYSIS OF CARDIAC DEVELOPMENT OF MICE DEFICIENT IN SIGNALING BY SEMAFORINAS. 1.5: ANALYSIS OF MICE DEFICIENT FOR ENDOCARDIAL NRG1. 1.6: ANALYSIS OF MICE DEFICIENT FOR ENDOCARDIAL EPHRINB2. 2.1: PROTEOMIC IDENTIFICATION OF SECRETED NOTCH-DEPENDENT FACTORS. 2.2: CHIP-SEQ WITH EMBRYONIC ENDOCARDIUM CELLS. 3.1: ANALYSIS OF WNT EXPRESSION AND FUNCTION IN JAG1-DEFICIENT MICE. 3.2: STUDY OF THE FUNCTION OF JAG1 AND JAG2 IN THE REMODELING OF OFT AND VALVULAR MORPHOGENESIS. 4.2: ULTRASECUENCIACION OF NOTCH IN LVNC AND BAV. 4,1-4,2: ANALYSIS OF CARDIAC REGENERATION OF MUTANTS FOR MDK-A, CAV-1 AND CAVIN GENERATED BY CRISPR/CAS9. _x000D_ Expected Results: 1) ESTABLISH THE FUNCTION OF NOTCH IN VENTRICULAR COMPACTION; 2) IDENTIFY THE DEFECT IN CARDIOMIOCYTIC DIFFERENTIATION OF MUTANT HIPSCS FOR MIB1; 3) DETERMINE THE FUNCTION OF GPR126, SEMAFORINAS AND NRG1 IN VENTRICULAR DEVELOPMENT; 4) IDENTIFY SECRETED NOTCH-DEPENDENT FACTORS DURING CARDIAC DEVELOPMENT; 5) IDENTIFY GENES REGULATED BY NOTCH DURING CARDIOGENESIS; 6) EPHRINB2 FUNCTION IN CORONARY VASCULATURE; 7) NOTCH IN OFT AND VALVULAR MORPHOGENESIS; 8) NOTCH AS A GENETIC MARKER OF LVNC AND BAV; 9) FUNCTION OF MDK-A, CAV-1 AND CAVIN IN CARDIAC REGENERATION. _x000D_ relevance: THIS PROJECT WILL ADVANCE KNOWLEDGE OF THE MECHANISMS UNDERLYING LVNC (AND RELATED MYOCARDIOPATHIES) AND BAV, AND HELP DESIGN NEW PREVENTIVE AND/OR THERAPEUTIC STRATEGIES. (English) | |||||||||||||||
| Property / summary: BACKGROUND: CARDIAC DEVELOPMENT RESULTS FROM THE INTEGRATED ACTION OF INTERCELLULAR SIGNALS, EPIGENETIC AND TRANSCRIPTIONAL REGULATORS. THE COORDINATED ACTION OF THESE FACTORS REGULATES THE PROCESSES OF PROLIFERATION, PATTERN FORMATION AND CELL DIFFERENTIATION THAT ORIGINATE THE ADULT HEART, AND THEIR ALTERATION RESULTS IN CONGENITAL HEART DISEASE (CHD) THAT IMPACT ON NEONATAL OR ADULT LIFE. _x000D_ objectives: STUDY THE ROLE OF INTERCELLULAR SIGNALLING IN (1) THE DEVELOPMENT AND PATHOLOGY OF CARDIAC VENTRICLES AND CORONARY VASCULATURE, (2) DEVELOPMENT AND VALVE PATHOLOGY, AND (3) CARDIAC REGENERATION. _x000D_ hypotheses: IDENTIFYING THE MECHANISM OF ACTION OF SIGNALING PATHWAYS ESSENTIAL FOR CARDIAC DEVELOPMENT IS CRUCIAL FOR UNDERSTANDING ETIOLOGY AND DEVELOPING TREATMENTS FOR HDC. _x000D_ SPECIFIC objectives: CHARACTERISE: 1.1: MICE WITH MIB1 MUTATIONS CAUSING NON-COMPACTED MYOCARDIOPATHY (NCML). 1.2: CARDIAC DIFFERENTIATION OF HUMAN INDUCED PROGENITOR CELLS (HIPSC) MUTANT FOR MIB1. 1,3-1,5: THE FUNCTION OF GPR126 (1.3), SEMAFORINAS (1.4) AND NRG1 (1.5) IN CARDIAC DEVELOPMENT. 1.6: EPHRINB2 IN THE DEVELOPMENT OF CORONARY VASCULATURE. 2.1: NOTCH’S DEPENDENT SECRETOMA IN CARDIAC DEVELOPMENT. 2.2: GENES REGULATED BY NOTCH DURING CARDIAC DEVELOPMENT. 3.1: WNT’S ROLE IN THE VALVE DEVELOPMENT DEPENDENT ON JAG1/NOTCH1. 3.2: JAG1 AND JAG2 FUNCTION IN THE REMODELING OF THE OUTPUT TRACT (OFT) AND VALVE MORPHOGENESIS. 3.3: THE INVOLVEMENT OF NOTCH IN LVNC AND BAV (BICUSPIDE AORTICA VALVE). 4,1-4,2: FUNCTION OF MDK-A (4.1), CAV-1 AND CAVIN (4.2) IN THE CARDIAC REGENERATION OF THE ZEBRAFISH. _x000D_ Methodology: 1.1: ANALYSIS OF MICE CARRYING MIB1 V943F AND R530X MUTATIONS. 1.2: CARDIOMYOCYTIC DIFFERENTIATION OF HIPSC WITH MIB1 MUTATIONS. 1.3: CARDIAC PHENOTYPE OF MICE WITH FALTA- OR EXCESS-OF-FUNCTION OF ENDOCARDIAL GPR126. 1.4: GENERATION AND ANALYSIS OF CARDIAC DEVELOPMENT OF MICE DEFICIENT IN SIGNALING BY SEMAFORINAS. 1.5: ANALYSIS OF MICE DEFICIENT FOR ENDOCARDIAL NRG1. 1.6: ANALYSIS OF MICE DEFICIENT FOR ENDOCARDIAL EPHRINB2. 2.1: PROTEOMIC IDENTIFICATION OF SECRETED NOTCH-DEPENDENT FACTORS. 2.2: CHIP-SEQ WITH EMBRYONIC ENDOCARDIUM CELLS. 3.1: ANALYSIS OF WNT EXPRESSION AND FUNCTION IN JAG1-DEFICIENT MICE. 3.2: STUDY OF THE FUNCTION OF JAG1 AND JAG2 IN THE REMODELING OF OFT AND VALVULAR MORPHOGENESIS. 4.2: ULTRASECUENCIACION OF NOTCH IN LVNC AND BAV. 4,1-4,2: ANALYSIS OF CARDIAC REGENERATION OF MUTANTS FOR MDK-A, CAV-1 AND CAVIN GENERATED BY CRISPR/CAS9. _x000D_ Expected Results: 1) ESTABLISH THE FUNCTION OF NOTCH IN VENTRICULAR COMPACTION; 2) IDENTIFY THE DEFECT IN CARDIOMIOCYTIC DIFFERENTIATION OF MUTANT HIPSCS FOR MIB1; 3) DETERMINE THE FUNCTION OF GPR126, SEMAFORINAS AND NRG1 IN VENTRICULAR DEVELOPMENT; 4) IDENTIFY SECRETED NOTCH-DEPENDENT FACTORS DURING CARDIAC DEVELOPMENT; 5) IDENTIFY GENES REGULATED BY NOTCH DURING CARDIOGENESIS; 6) EPHRINB2 FUNCTION IN CORONARY VASCULATURE; 7) NOTCH IN OFT AND VALVULAR MORPHOGENESIS; 8) NOTCH AS A GENETIC MARKER OF LVNC AND BAV; 9) FUNCTION OF MDK-A, CAV-1 AND CAVIN IN CARDIAC REGENERATION. _x000D_ relevance: THIS PROJECT WILL ADVANCE KNOWLEDGE OF THE MECHANISMS UNDERLYING LVNC (AND RELATED MYOCARDIOPATHIES) AND BAV, AND HELP DESIGN NEW PREVENTIVE AND/OR THERAPEUTIC STRATEGIES. (English) / rank | |||||||||||||||
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| Property / summary: BACKGROUND: CARDIAC DEVELOPMENT RESULTS FROM THE INTEGRATED ACTION OF INTERCELLULAR SIGNALS, EPIGENETIC AND TRANSCRIPTIONAL REGULATORS. THE COORDINATED ACTION OF THESE FACTORS REGULATES THE PROCESSES OF PROLIFERATION, PATTERN FORMATION AND CELL DIFFERENTIATION THAT ORIGINATE THE ADULT HEART, AND THEIR ALTERATION RESULTS IN CONGENITAL HEART DISEASE (CHD) THAT IMPACT ON NEONATAL OR ADULT LIFE. _x000D_ objectives: STUDY THE ROLE OF INTERCELLULAR SIGNALLING IN (1) THE DEVELOPMENT AND PATHOLOGY OF CARDIAC VENTRICLES AND CORONARY VASCULATURE, (2) DEVELOPMENT AND VALVE PATHOLOGY, AND (3) CARDIAC REGENERATION. _x000D_ hypotheses: IDENTIFYING THE MECHANISM OF ACTION OF SIGNALING PATHWAYS ESSENTIAL FOR CARDIAC DEVELOPMENT IS CRUCIAL FOR UNDERSTANDING ETIOLOGY AND DEVELOPING TREATMENTS FOR HDC. _x000D_ SPECIFIC objectives: CHARACTERISE: 1.1: MICE WITH MIB1 MUTATIONS CAUSING NON-COMPACTED MYOCARDIOPATHY (NCML). 1.2: CARDIAC DIFFERENTIATION OF HUMAN INDUCED PROGENITOR CELLS (HIPSC) MUTANT FOR MIB1. 1,3-1,5: THE FUNCTION OF GPR126 (1.3), SEMAFORINAS (1.4) AND NRG1 (1.5) IN CARDIAC DEVELOPMENT. 1.6: EPHRINB2 IN THE DEVELOPMENT OF CORONARY VASCULATURE. 2.1: NOTCH’S DEPENDENT SECRETOMA IN CARDIAC DEVELOPMENT. 2.2: GENES REGULATED BY NOTCH DURING CARDIAC DEVELOPMENT. 3.1: WNT’S ROLE IN THE VALVE DEVELOPMENT DEPENDENT ON JAG1/NOTCH1. 3.2: JAG1 AND JAG2 FUNCTION IN THE REMODELING OF THE OUTPUT TRACT (OFT) AND VALVE MORPHOGENESIS. 3.3: THE INVOLVEMENT OF NOTCH IN LVNC AND BAV (BICUSPIDE AORTICA VALVE). 4,1-4,2: FUNCTION OF MDK-A (4.1), CAV-1 AND CAVIN (4.2) IN THE CARDIAC REGENERATION OF THE ZEBRAFISH. _x000D_ Methodology: 1.1: ANALYSIS OF MICE CARRYING MIB1 V943F AND R530X MUTATIONS. 1.2: CARDIOMYOCYTIC DIFFERENTIATION OF HIPSC WITH MIB1 MUTATIONS. 1.3: CARDIAC PHENOTYPE OF MICE WITH FALTA- OR EXCESS-OF-FUNCTION OF ENDOCARDIAL GPR126. 1.4: GENERATION AND ANALYSIS OF CARDIAC DEVELOPMENT OF MICE DEFICIENT IN SIGNALING BY SEMAFORINAS. 1.5: ANALYSIS OF MICE DEFICIENT FOR ENDOCARDIAL NRG1. 1.6: ANALYSIS OF MICE DEFICIENT FOR ENDOCARDIAL EPHRINB2. 2.1: PROTEOMIC IDENTIFICATION OF SECRETED NOTCH-DEPENDENT FACTORS. 2.2: CHIP-SEQ WITH EMBRYONIC ENDOCARDIUM CELLS. 3.1: ANALYSIS OF WNT EXPRESSION AND FUNCTION IN JAG1-DEFICIENT MICE. 3.2: STUDY OF THE FUNCTION OF JAG1 AND JAG2 IN THE REMODELING OF OFT AND VALVULAR MORPHOGENESIS. 4.2: ULTRASECUENCIACION OF NOTCH IN LVNC AND BAV. 4,1-4,2: ANALYSIS OF CARDIAC REGENERATION OF MUTANTS FOR MDK-A, CAV-1 AND CAVIN GENERATED BY CRISPR/CAS9. _x000D_ Expected Results: 1) ESTABLISH THE FUNCTION OF NOTCH IN VENTRICULAR COMPACTION; 2) IDENTIFY THE DEFECT IN CARDIOMIOCYTIC DIFFERENTIATION OF MUTANT HIPSCS FOR MIB1; 3) DETERMINE THE FUNCTION OF GPR126, SEMAFORINAS AND NRG1 IN VENTRICULAR DEVELOPMENT; 4) IDENTIFY SECRETED NOTCH-DEPENDENT FACTORS DURING CARDIAC DEVELOPMENT; 5) IDENTIFY GENES REGULATED BY NOTCH DURING CARDIOGENESIS; 6) EPHRINB2 FUNCTION IN CORONARY VASCULATURE; 7) NOTCH IN OFT AND VALVULAR MORPHOGENESIS; 8) NOTCH AS A GENETIC MARKER OF LVNC AND BAV; 9) FUNCTION OF MDK-A, CAV-1 AND CAVIN IN CARDIAC REGENERATION. _x000D_ relevance: THIS PROJECT WILL ADVANCE KNOWLEDGE OF THE MECHANISMS UNDERLYING LVNC (AND RELATED MYOCARDIOPATHIES) AND BAV, AND HELP DESIGN NEW PREVENTIVE AND/OR THERAPEUTIC STRATEGIES. (English) / qualifier | |||||||||||||||
point in time: 12 October 2021
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Revision as of 12:29, 12 October 2021
Project Q3135099 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | No label defined |
Project Q3135099 in Spain |
Statements
242,000.0 Euro
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484,000.0 Euro
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50.0 percent
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30 December 2016
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29 December 2020
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FUNDACION CENTRO NAL DE INV. CARDIOVASCULARES CARLOS III
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40°25'0.12"N, 3°42'12.89"W
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28079
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ANTECEDENTES: EL DESARROLLO CARDIACO RESULTA DE LA ACCION INTEGRADA DE SEÑALES INTERCELULARES, REGULADORES EPIGENETICOS Y TRANSCRIPCIONALES. LA ACCION COORDINADA DE ESTOS FACTORES REGULA LOS PROCESOS DE PROLIFERACION, FORMACION DE PATRON Y DIFERENCIACION CELULAR QUE ORIGINAN EL CORAZON ADULTO, Y SU ALTERACION DA LUGAR A ENFERMEDADES CARDIACAS CONGENITAS (CHD) QUE IMPACTAN EN LA VIDA NEONATAL O ADULTA. _x000D_ OBJETIVOS: ESTUDIAR EL PAPEL DE LA SEÑALIZACION INTERCELULAR EN (1) EL DESARROLLO Y LA PATOLOGIA DE LOS VENTRICULOS CARDIACOS Y DE LA VASCULATURA CORONARIA, (2) EL DESARROLLO Y LA PATOLOGIA VALVULAR, Y (3) LA REGENERACION CARDIACA. _x000D_ HIPOTESIS: IDENTIFICAR EL MECANISMO DE ACCION DE LAS VIAS DE SEÑALIZACION ESENCIALES PARA EL DESARROLLO CARDIACO ES CRUCIAL PARA ENTENDER LA ETIOLOGIA Y DESARROLLAR TRATAMIENTOS PARA LAS CHD. _x000D_ OBJETIVOS ESPECIFICOS: CARACTERIZAR: 1.1: RATONES CON MUTACIONES EN MIB1 CAUSANTES DE MIOCARDIOPATIA NO COMPACTADA (LVNC). 1.2: LA DIFERENCIACION CARDIACA DE CELULAS PROGENITORAS INDUCIDAS HUMANAS (HIPSC) MUTANTES PARA MIB1. 1.3-1.5: LA FUNCION DE GPR126 (1.3), SEMAFORINAS (1.4) Y NRG1 (1.5) EN EL DESARROLLO CARDIACO. 1.6: EPHRINB2 EN EL DESARROLLO DE LA VASCULATURA CORONARIA. 2.1: EL SECRETOMA DEPENDIENTE DE NOTCH EN EL DESARROLLO CARDIACO. 2.2: LOS GENES REGULADOS POR NOTCH DURANTE EL DESARROLLO CARDIACO. 3.1: FUNCION DE WNT EN EL DESARROLLO VALVULAR DEPENDIENTE DE JAG1/NOTCH1. 3.2: FUNCION DE JAG1 Y JAG2 EN EL REMODELADO DEL TRACTO DE SALIDA (OFT) Y LA MORFOGENESIS VALVULAR. 3.3: LA IMPLICACION DE NOTCH EN LVNC Y BAV (VALVULA AORTICA BICUSPIDE). 4.1-4.2: FUNCION DE MDK-A (4.1), CAV-1 Y CAVIN (4.2) EN LA REGENERACION CARDIACA DEL PEZ CEBRA. _x000D_ METODOLOGIA: 1.1: ANALISIS DE RATONES PORTADORES DE LAS MUTACIONES EN MIB1 V943F Y R530X. 1.2: DIFERENCIACION CARDIOMIOCITICA DE HIPSC CON MUTACIONES EN MIB1. 1.3: FENOTIPO CARDIACO DE RATONES CON FALTA- O EXCESO-DE-FUNCION DE GPR126 ENDOCARDIAL. 1.4: GENERACION Y ANALISIS DEL DESARROLLO CARDIACO DE RATONES DEFICIENTES EN SEÑALIZACION POR SEMAFORINAS. 1.5: ANALISIS DE RATONES DEFICIENTES PARA NRG1 ENDOCARDIAL. 1.6: ANALISIS DE RATONES DEFICIENTES PARA EPHRINB2 ENDOCARDIAL. 2.1: IDENTIFICACION PROTEOMICA DE LOS FACTORES SECRETADOS DEPENDIENTES DE NOTCH. 2.2: CHIP-SEQ CON CELULAS DEL ENDOCARDIO EMBRIONARIO. 3.1: ANALISIS DE LA EXPRESION Y FUNCION DE WNT EN RATONES DEFICIENTES PARA JAG1. 3.2: ESTUDIO DE LA FUNCION DE JAG1 Y JAG2 EN EL REMODELADO DEL OFT Y LA MORFOGENESIS VALVULAR. 4.2: ULTRASECUENCIACION DE NOTCH EN LVNC Y BAV. 4.1-4.2: ANALISIS DE LA REGENERACION CARDIACA DE MUTANTES PARA MDK-A, CAV-1 Y CAVIN GENERADOS MEDIANTE CRISPR/CAS9. _x000D_ RESULTADOS ESPERADOS: 1) ESTABLECER LA FUNCION DE NOTCH EN LA COMPACTACION VENTRICULAR; 2) IDENTIFICAR EL DEFECTO EN DIFERENCIACION CARDIOMIOCITICA DE LAS HIPSC MUTANTES PARA MIB1; 3) DETERMINAR LA FUNCION DE GPR126, SEMAFORINAS Y NRG1 EN EL DESARROLLO VENTRICULAR; 4) IDENTIFICAR LOS FACTORES SECRETADOS DEPENDIENTES DE NOTCH DURANTE EL DESARROLLO CARDIACO; 5) IDENTIFICAR LOS GENES REGULADOS POR NOTCH DURANTE CARDIOGENESIS; 6) FUNCION DE EPHRINB2 EN LA VASCULATURA CORONARIA; 7) NOTCH EN LA MORFOGENESIS DEL OFT Y VALVULAR; 8) NOTCH COMO UN MARCADOR GENETICO DE LA LVNC Y BAV; 9) FUNCION DE MDK-A, CAV-1 Y CAVIN EN LA REGENERACION CARDIACA. _x000D_ RELEVANCIA: ESTE PROYECTO AVANZARA EN EL CONOCIMIENTO DE LOS MECANISMOS SUBYACENTES A LA LVNC (Y MIOCARDIOPATIAS RELACIONADAS) Y BAV, Y AYUDARA A DISEÑAR NUEVAS ESTRATEGIAS PREVENTIVAS Y/O TERAPEUTICAS. (Spanish)
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BACKGROUND: CARDIAC DEVELOPMENT RESULTS FROM THE INTEGRATED ACTION OF INTERCELLULAR SIGNALS, EPIGENETIC AND TRANSCRIPTIONAL REGULATORS. THE COORDINATED ACTION OF THESE FACTORS REGULATES THE PROCESSES OF PROLIFERATION, PATTERN FORMATION AND CELL DIFFERENTIATION THAT ORIGINATE THE ADULT HEART, AND THEIR ALTERATION RESULTS IN CONGENITAL HEART DISEASE (CHD) THAT IMPACT ON NEONATAL OR ADULT LIFE. _x000D_ objectives: STUDY THE ROLE OF INTERCELLULAR SIGNALLING IN (1) THE DEVELOPMENT AND PATHOLOGY OF CARDIAC VENTRICLES AND CORONARY VASCULATURE, (2) DEVELOPMENT AND VALVE PATHOLOGY, AND (3) CARDIAC REGENERATION. _x000D_ hypotheses: IDENTIFYING THE MECHANISM OF ACTION OF SIGNALING PATHWAYS ESSENTIAL FOR CARDIAC DEVELOPMENT IS CRUCIAL FOR UNDERSTANDING ETIOLOGY AND DEVELOPING TREATMENTS FOR HDC. _x000D_ SPECIFIC objectives: CHARACTERISE: 1.1: MICE WITH MIB1 MUTATIONS CAUSING NON-COMPACTED MYOCARDIOPATHY (NCML). 1.2: CARDIAC DIFFERENTIATION OF HUMAN INDUCED PROGENITOR CELLS (HIPSC) MUTANT FOR MIB1. 1,3-1,5: THE FUNCTION OF GPR126 (1.3), SEMAFORINAS (1.4) AND NRG1 (1.5) IN CARDIAC DEVELOPMENT. 1.6: EPHRINB2 IN THE DEVELOPMENT OF CORONARY VASCULATURE. 2.1: NOTCH’S DEPENDENT SECRETOMA IN CARDIAC DEVELOPMENT. 2.2: GENES REGULATED BY NOTCH DURING CARDIAC DEVELOPMENT. 3.1: WNT’S ROLE IN THE VALVE DEVELOPMENT DEPENDENT ON JAG1/NOTCH1. 3.2: JAG1 AND JAG2 FUNCTION IN THE REMODELING OF THE OUTPUT TRACT (OFT) AND VALVE MORPHOGENESIS. 3.3: THE INVOLVEMENT OF NOTCH IN LVNC AND BAV (BICUSPIDE AORTICA VALVE). 4,1-4,2: FUNCTION OF MDK-A (4.1), CAV-1 AND CAVIN (4.2) IN THE CARDIAC REGENERATION OF THE ZEBRAFISH. _x000D_ Methodology: 1.1: ANALYSIS OF MICE CARRYING MIB1 V943F AND R530X MUTATIONS. 1.2: CARDIOMYOCYTIC DIFFERENTIATION OF HIPSC WITH MIB1 MUTATIONS. 1.3: CARDIAC PHENOTYPE OF MICE WITH FALTA- OR EXCESS-OF-FUNCTION OF ENDOCARDIAL GPR126. 1.4: GENERATION AND ANALYSIS OF CARDIAC DEVELOPMENT OF MICE DEFICIENT IN SIGNALING BY SEMAFORINAS. 1.5: ANALYSIS OF MICE DEFICIENT FOR ENDOCARDIAL NRG1. 1.6: ANALYSIS OF MICE DEFICIENT FOR ENDOCARDIAL EPHRINB2. 2.1: PROTEOMIC IDENTIFICATION OF SECRETED NOTCH-DEPENDENT FACTORS. 2.2: CHIP-SEQ WITH EMBRYONIC ENDOCARDIUM CELLS. 3.1: ANALYSIS OF WNT EXPRESSION AND FUNCTION IN JAG1-DEFICIENT MICE. 3.2: STUDY OF THE FUNCTION OF JAG1 AND JAG2 IN THE REMODELING OF OFT AND VALVULAR MORPHOGENESIS. 4.2: ULTRASECUENCIACION OF NOTCH IN LVNC AND BAV. 4,1-4,2: ANALYSIS OF CARDIAC REGENERATION OF MUTANTS FOR MDK-A, CAV-1 AND CAVIN GENERATED BY CRISPR/CAS9. _x000D_ Expected Results: 1) ESTABLISH THE FUNCTION OF NOTCH IN VENTRICULAR COMPACTION; 2) IDENTIFY THE DEFECT IN CARDIOMIOCYTIC DIFFERENTIATION OF MUTANT HIPSCS FOR MIB1; 3) DETERMINE THE FUNCTION OF GPR126, SEMAFORINAS AND NRG1 IN VENTRICULAR DEVELOPMENT; 4) IDENTIFY SECRETED NOTCH-DEPENDENT FACTORS DURING CARDIAC DEVELOPMENT; 5) IDENTIFY GENES REGULATED BY NOTCH DURING CARDIOGENESIS; 6) EPHRINB2 FUNCTION IN CORONARY VASCULATURE; 7) NOTCH IN OFT AND VALVULAR MORPHOGENESIS; 8) NOTCH AS A GENETIC MARKER OF LVNC AND BAV; 9) FUNCTION OF MDK-A, CAV-1 AND CAVIN IN CARDIAC REGENERATION. _x000D_ relevance: THIS PROJECT WILL ADVANCE KNOWLEDGE OF THE MECHANISMS UNDERLYING LVNC (AND RELATED MYOCARDIOPATHIES) AND BAV, AND HELP DESIGN NEW PREVENTIVE AND/OR THERAPEUTIC STRATEGIES. (English)
12 October 2021
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Madrid
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Identifiers
SAF2016-78370-R
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