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BFU2011-22570

Financiado

CARACTERIZACION FUNCIONAL DE LA VIA DE SEÑALIZACION DE LOS RECEPTORES DE FACTORE...

CARACTERIZACION FUNCIONAL DE LA VIA DE SEÑALIZACION DE LOS RECEPTORES DE FACTORES DE CRECIMIENTO EPIDERMICOS (EGFR) DURANTE LA REGENERACION Y HOMEOSTASIS EN PLANARIAS PEOPLE HAVE BEEN ALWAYS FASCINATED BY THE CAPACITY SHOWN BY SOME ANIMALS TO REGENERATE INJURED OR LOST BODY PARTS. MANY PEOPLE ARE AWARE OF THE ABILITIES BY SOME SALAMANDERS, LIZARDS AND ZEBRAFISH TO REGENERATE LIMBS, TAILS, RETIN... ver más

01/01/2011

73K€

Presupuesto del proyecto: 73K€

Líder del proyecto

UNIVERSIDAD DE BARCELONA No se ha especificado una descripción o un objeto social para esta compañía.

Total investigadores 327

Financiación concedida El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2011-01-01 No tenemos la información de la convocatoria

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Líder del proyecto

UNIVERSIDAD DE BARCELONA No se ha especificado una descripción o un objeto social para esta compañía.

Total investigadores 327

Presupuesto del proyecto 73K€

Descripción del proyecto PEOPLE HAVE BEEN ALWAYS FASCINATED BY THE CAPACITY SHOWN BY SOME ANIMALS TO REGENERATE INJURED OR LOST BODY PARTS. MANY PEOPLE ARE AWARE OF THE ABILITIES BY SOME SALAMANDERS, LIZARDS AND ZEBRAFISH TO REGENERATE LIMBS, TAILS, RETINAS, JAWS, FINS OR HEARTS. OUTSIDE VERTEBRATES, SOME CNIDARIANS, ANNELIDS, INSECTS AND ECHINODERMS DISPLAY DIFFERENT DEGREES OF REGENERATIVE POWER. IN THE LAST YEARS, AND BECAUSE OF THE EMERGENCE OF THE FIELDS OF STEM CELLS AND REGENERATIVE MEDICINE, THE SCIENTIFIC COMMUNITY HAS TURNED ITS EYES TOWARDS THOSE CLASSICAL MODELS TO STUDY REGENERATION. FRESHWATER PLANARIANS ARE ONE OF SUCH CLASSICAL MODELS. THESE ANIMALS SHOW ALMOST UNBEATABLE REGENERATIVE CAPACITIES AS THEY CAN REGENERATE A WHOLE ANIMAL FROM A TINY PIECE OF THEIR BODIES. PLANARIAN REGENERATION DEPENDS UPON A UNIQUE POPULATION OF PLURIPOTENT ADULT STEM CELLS, CALLED NEOBLASTS. UPON AMPUTATION, NEOBLASTS PROLIFERATE AND DIFFERENTIATE INTO ALL MISSING CELL TYPES, INCLUDING GERM CELLS, IN SEXUAL SPECIES. THEREFORE, PLANARIANS OFFER THE OPPORTUNITY TO STUDY NOT ONLY HOW THE MISSING PARTS ARE RE-GROWN AND PROPERLY PATTERNED WITH THE PRE-EXISTING TISSUES, BUT ALSO CONSTITUTE AN EXCELLENT MODEL IN WHICH TO STUDY THE BEHAVIOR OF PLURIPOTENT STEM CELLS IN VIVO. SIMILARLY TO DEVELOPMENT, THE PROCESS OF REGENERATION REQUIRES THAT CELLS ACCURATELY SENSE AND RESPOND TO THEIR EXTERNAL ENVIRONMENT. THUS, INTRINSIC CUES MUST BE INTEGRATED WITH SIGNALS FROM THE SURROUNDING ENVIRONMENT TO ENSURE APPROPRIATE TEMPORAL AND SPATIAL REGULATION OF TISSUE REGENERATION. IDENTIFYING THE SIGNALLING PATHWAYS THAT CONTROL THESE EVENTS WILL NOT ONLY PROVIDE INSIGHTS INTO A FASCINATING BIOLOGICAL PHENOMENON BUT MAY ALSO YIELD NEW MOLECULAR TARGETS FOR USE IN REGENERATIVE MEDICINE. ONE OF SUCH SIGNALLING PATHWAYS IS THE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR). THIS PATHWAY PLAYS IMPORTANT ROLES IN REGENERATION IN INSECTS, ZEBRAFISH AND MAMMALIAN LIVER BY REGULATING PATTERNING AND CELL PROLIFERATION AND MIGRATION. MOREOVER EGFR SIGNALLING CONTROLS NEURAL DIFFERENTIATION IN MANY ANIMALS, INCLUDING MAMMALS AND IT IS A PATHWAY USUALLY OVERACTIVATED IN MOST HUMAN CANCERS. IN OUR LABORATORY WE HAVE IDENTIFIED THREE HOMOLOGUES TO EGFRS IN THE PLANARIAN SCHMIDTEA MEDITERRANEA. OUR FIRST RESULTS INDICATE THAT THEY ARE EXPRESSED IN DIFFERENT CELL TYPES, INCLUDING NEOBLASTS AND THAT THEY ARE REQUIRED FOR PHARYNX REGENERATION, CELL DIFFERENTIATION, BLASTEMA GROWTH AND PROPER MORPHOGENESIS. THE MAIN GOAL OF THIS PROPOSAL IS TO STUDY IN DETAIL THE FUNCTION OF THE EGFR SIGNALLING PATHWAY DURING PLANARIAN REGENERATION AND HOMEOSTASIS. FOLLOWING UP WITH THE RESULTS WE HAVE OBTAINED IN THE LAST TWO YEARS, THE SPECIFIC AIMS HERE ARE:1.- TO CHARACTERIZE HOW SMED-EGFR-3 CONTROLS NEOBLAST DIFFERENTIATION AND BLASTEMA GROWTH DURING PLANARIAN REGENERATION AND TO IDENTIFY THE TARGET DOWNSTREAM GENES INVOLVED.2.- TO CHARACTERIZE HOW SMED-EGFR-1 CONTROLS EYE PIGMENT DIFFERENTIATION, PHARYNX REGENERATION AND MORPHOGENESIS IN INTACT AND REGENERATING PLANARIANS AND TO IDENTIFY THE TARGET DOWNSTREAM GENES INVOLVED.3.- TO SEARCH FOR THE PLANARIAN HOMOLOGUES OF EPIDERMAL GROWTH FACTORS.4.- TO CHARACTERIZE THE FUNCTION OF PLANARIAN RHOMBOIDS ON THE EGFR SIGNALLING PATHWAY.5.- FINALLY, A SECONDARY IMPORTANT GOAL OF THIS PROJECT IS TO CHARACTERIZE THE FUNCTION OF A COLLECTION OF NEUROTRANSMITTER, PEPTIDE AND HORMONE RECEPTORS FROM A 454 PYROSEQUENCING TRANSCRIPTOME PROJECT. LANARIA\HORMONAS\RECEPTORES\NEUROTRANSMISORES\DIFERENCIACION\NEUROGENESIS\CELULAS MADRE\FACTOR DE CRECIMIENTO EPIDERMICO\REGENERACION

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