DESVELANDO LA COORDINACION ENTRE LA DINAMICA DE LOS PROGENITORES Y LA MORFOGENES...
DESVELANDO LA COORDINACION ENTRE LA DINAMICA DE LOS PROGENITORES Y LA MORFOGENESIS DEL TEJIDO DURANTE EL DESARROLLO NEURAL: HACIA UNA PERSPECTIVA EN 4D
THE ASSEMBLY OF FUNCTIONAL NEURAL CIRCUITS REQUIRES THE SPECIFICATION OF NEURONAL IDENTITIES AND THE EXECUTION OF DEVELOPMENTAL PROGRAMS THAT ESTABLISH PRECISE NEURAL NETWORK WIRING, THE PRESENT PROJECT USES THE EMBRYONIC ZEBRAFIS...
THE ASSEMBLY OF FUNCTIONAL NEURAL CIRCUITS REQUIRES THE SPECIFICATION OF NEURONAL IDENTITIES AND THE EXECUTION OF DEVELOPMENTAL PROGRAMS THAT ESTABLISH PRECISE NEURAL NETWORK WIRING, THE PRESENT PROJECT USES THE EMBRYONIC ZEBRAFISH HINDBRAIN AS A MODEL SYSTEM, IN ORDER TO STUDY HOW CELLULAR COMPARTMENTS OPERATE DURING BRAIN DEVELOPMENT, AND HOW TISSUE MORPHOGENESIS AND CELL SPECIFICATION ARE COORDINATED DURING EMBRYONIC DEVELOPMENT, OUR AIM IS TO UNDERSTAND HOW SPATIOTEMPORALLY COORDINATED CELL PROGENITOR SPECIFICATION AND DIFFERENTIATION OCCURS ALONGSIDE MORPHOGENESIS TO CONSTRUCT THE FUNCTIONAL BRAIN, THUS, WE NEED TO BLEND THE INFORMATION PROVIDED BY MORPHOGENESIS AND TISSUE GROWTH STUDIES -BALANCING PROGENITORS VS, DIFFERENTIATED CELLS-, WITH THE RECONSTRUCTION OF CELL LINEAGES, WITH THE DEMAND TO INCORPORATE THE TIME AS A CRUCIAL FACTOR, IN ORDER TO DO THIS, WE WANT TO: I) ELUCIDATE HOW TISSUE GROWTH AND CELL PROLIFERATION AND DIFFERENTIATION ARE INTERTWINED AND INFLUENCE CELL FATE; II) UNVEIL HOW INDIVIDUAL PROGENITORS BEHAVE THROUGHOUT PATTERNING, PROLIFERATION, AND MORPHOGENESIS, THEREFORE RECONSTRUCTING THE CELL LINEAGE RELATIONSHIPS; AND III) DISCERN THE INTERACTIONS AMONG DETERMINATIVE FACTORS THAT DICTATE THE COMPETENCE OF PROGENITORS AND THE SELECTION OF SPECIFIC CELL FATES TO CONTROL THE DISTINCT CELLULAR BEHAVIORS, TO TACKLE THESE QUESTIONS OUR SPECIFIC AIMS ARE THE FOLLOWING: I) UNCOVERING THE CLONAL DYNAMICS OF THE HINDBRAIN: BALANCING PROLIFERATION AND DIFFERENTIATION, BY LIFE-MONITORING THE OVERALL HINDBRAIN GROWTH AND THE GROWTH OF SPECIFIC PROGENITORS, USING GENETIC CLONAL ANALYSES COMBINED WITH A MACHINE LEARNING PLATFORM; II) DECIPHERING HOW CELL DIVERSITY IS GENERATED IN THE DEVELOPING HINDBRAIN; UNDERSTANDING HOW THE PROGENITOR/NEUROGENIC/GLIOGENIC CAPACITIES ARE COORDINATELY ALLOCATED TO SPECIFIC TERRITORIES OF THE HINDBRAIN OVER TIME, WE WILL COMBINE FUNCTIONAL STUDIES, GENETIC CELL ABLATION, AND HIGH-RESOLUTION IN VIVO IMAGING FOR CELL LINEAGE STUDIES; III) DISSECTING THE GENE REGULATORY NETWORKS (GRN) THAT RESTRICT PROGENITOR VS, NEUROGENIC CAPACITIES, BY IN SILICO ANALYSES OF CIS-REGULATORY REGIONS AND TRANSCRIPTOMICS TO UNVEIL TRANSCRIPTIONAL ACTIVATION SIGNATURES THAT FORESHADOW THE DYNAMIC PROGENITOR CELL STATES,THE RESULTS OF THIS PROJECT WILL PROVIDE INSIGHTS INTO HOW BRAIN PROGENITORS COMMIT AND HOW THEY BEHAVE ONCE COMMITTED TO A GIVEN FATE, AND WILL HELP TO FILL THE VOID BETWEEN GENE REGULATORY NETWORKS AND TISSUE ARCHITECTURE, THUS UPON COMPLETION, IT WILL PROVIDE US WITH A BETTER COMPREHENSION OF THE ONTOGENY OF NEUROLOGICAL DISORDERS AND MUCH NEEDED FOUNDATIONAL KNOWLEDGE FOR THE PRODUCTION OF STEM CELL DERIVED NEURONS FOR THE THERAPEUTIC RECONSTRUCTION OF NEURAL CIRCUITS, HINDBRAIN SEGMENTATION\RHOMBOMERES\BOUNDARIES\COMPARTMENTS\CELL SPECIFICATION\GENE REGULATION\NEUROGENESIS\CELL LINEAGE\CLONAL GROWTH\MORPHOGENESISver más
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