Innovating Works

BFU2011-29490

Financiado
CONTROL GENETICO DE LA NEUROGENESIS Y LA REGIONALIZACION DE LA MEDULA ESPINAL DU...
CONTROL GENETICO DE LA NEUROGENESIS Y LA REGIONALIZACION DE LA MEDULA ESPINAL DURANTE EL DESARROLLO: FUNCIONES DE LOS GENES SOXD. DURING THE DEVELOPMENT OF THE CENTRAL NERVOUS SYSTEM (CNS), A LARGE NUMBER OF DIFFERENT NEURONS AND GLIAL CELLS ARE GENERATED FROM A SMALL POPULATION OF SELF-RENEWING STEM AND PROGENITOR CELLS. THE CORRECT COORDINATION OF THESE EV... DURING THE DEVELOPMENT OF THE CENTRAL NERVOUS SYSTEM (CNS), A LARGE NUMBER OF DIFFERENT NEURONS AND GLIAL CELLS ARE GENERATED FROM A SMALL POPULATION OF SELF-RENEWING STEM AND PROGENITOR CELLS. THE CORRECT COORDINATION OF THESE EVENTS REQUIRES TIGHT REGULATED SPATIO-TEMPORAL CONTROL. DISTINCT NEURONAL SUBTYPES EMERGE FROM PROGENITOR CELLS IN A PRECISE SPATIAL ORDER, PARTITIONING THE DORSO-VENTRAL (D-V) AXIS OF THE NEURAL TUBE INTO DISCRETE REGIONS THAT ARE OCCUPIED BY DIFFERENT NEURAL PRECURSORS AND NEURONAL SUBTYPES (JESSELL, 2000; DESSAUD ET AL., 2008). SEVERAL GENETIC AND EPIGENETIC PROGRAMMES THAT CONTROL CELL CYCLE PROGRESSION, CELL FATE SPECIFICATION AND NEURONAL DIFFERENTIATION HAVE BEEN UNRAVELLED. HOWEVER, LITTLE IS KNOWN ABOUT HOW THEY ARE INTERCONNECTED TO CORRECTLY REGULATE THE PROCESS OF NEUROGENESIS. THE HMG-BOX TRANSCRIPTION FACTORS OF THE SOX GENE FAMILY COULD BE AT THE CORE OF SOME OF THOSE PROCESSES, AS THEY HAVE ESSENTIAL REGULATORY FUNCTIONS DURING NEUROGENESIS IN THE CNS (WEGNER AND STOLT, 2005) INCLUDING: NEUROECTODERMAL COMPETENCE, SELF-RENEWAL AND PLURIPOTENCY OF NEURAL STEM-CELLS AND MACROGLIAL CELLS DIFFERENTIATION. WE HAVE RECENTLY ESTABLISHED THAT SOX5, ONE OF THE SOXD GROUP MEMBERS, CONTROLS THE TIMING OF CELL CYCLE EXIT IN NEURAL PRECURSORS, BY COUNTERACTING THE MITOTIC EFFECT OF THE WNT/BETA-CATENIN PATHWAY, AT LEAST IN THE DORSAL NEURAL TUBE (MARTINEZ-MORALES ET AL., 2010). MOREOVER, OUR WORK IN PROGRESS ALSO SUGGESTS THAT SOX5 CONTROLS THE CELL FATE SPECIFICATION OF DORSAL NEURAL PROGENITORS. HOWEVER, IT IS NOT CLEAR IF SOX5 EXERTS A SIMILAR CONTROL ON PROLIFERATION AND CELL SPECIFICATION ON VENTRAL NEURAL PROGENITORS AND IF OTHER SOXD FAMILY MEMBERS (SOX6 AND SOX13) COULD COLLABORATE WITH SOX5. FURTHERMORE, IT IS NOT KNOWN, IF SOXD GENES MODULATE THE PREDOMINANT SIGNALLING OF THE VENTRAL SPINAL CORD, I.E SHH SIGNALLING PATHWAY, AND HOW, IN TURN, CAN SOXD GENES EXPRESSION BE FINELY TUNED IN THE SPINAL CORD.IN THIS PROJECT, MOSTLY USING GAIN AND LACK OF FUNCTION EXPERIMENTS IN CHICK EMBRYOS WE PROPOSE: I) TO EXPLORE THE MECHANISM OF ACTION OF SOXD IN THE CONTROL OF CELL CYCLE EXIT OF VENTRAL PROGENITORS, FOCUSSING ON ELEMENTS OF THE WNT AND SHH PATHWAYS; II) TO ANALYSE WHETHER SOXD FACTORS ARE REQUIRED FOR THE ESTABLISHMENT AND/OR MAINTENANCE OF THE VENTRAL IDENTITY OF THE NEURAL PRECURSORS AND THE FLOOR PLATE; III) TO ANALYSE THE POSSIBLE REGULATION OF SOXD EXPRESSION BY EXTRACELLULAR SIGNALS (SHH, RETINOIC ACID AND BMP) AND BY MIRNAS (MORE INTERESTINGLY MIR-21).THE RESULTS THAT WILL EMANATE FROM THESE STUDIES WILL CONTRIBUTE DECISIVELY TO A BETTER UNDERSTANDING OF THE COORDINATION BETWEEN CELL-FATE SPECIFICATION AND NEUROGENESIS DURING THE SPINAL CORD DEVELOPMENT AND THE INTERPLAY OF WNT, SHH AND RETINOIC ACID SIGNALLING PATHWAYS WITH SOXD FACTORS TO COORDINATE THOSE ESSENTIAL PROCESSES. MBRION\SOXD\SHH\WNT\PATRON-DORSOVENTRAL\DIFERENCIACION\NEUROGENESIS\PROLIFERACION\MEDULA-ESPINAL\VERTEBRADO ver más
01/01/2011
CSIC
163K€
Perfil tecnológico estimado

Línea de financiación: concedida

El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2011-01-01
Presupuesto El presupuesto total del proyecto asciende a 163K€
Líder del proyecto
AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGA... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 2-3 552M