8/5/2011. TÁMOP–4.1.2-08/2/A/KMR-2009-0006 1 Development of Complex Curricula for Molecular Bionics and InfobionicsPrograms within a consortial* framework** Consortium leader PETER PAZMANYCATHOLIC UNIVERSITY Consortium members SEMMELWEISUNIVERSITY, DIALOG CAMPUS PUBLISHER The Project has been realisedwith the support of the European Union and has been co-financed by the European Social Fund *** **Molekuláris bionika és Infobionika Szakok tananyagának komplex fejlesztése konzorciumi keretben ***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg. PETER PAZMANY CATHOLIC UNIVERSITY SEMMELWEIS UNIVERSITY sote_logo.jpg dk_fejlec.gif INFOBLOKK 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2 Peter Pazmany Catholic University Faculty of Information Technology BASICS OF NEUROBIOLOGY DEVELOPMENT OF THE NERVOUS SYSTEM www.itk.ppke.hu Neurobiológia alapjai (Idegrendszerfejlődése) ZSOLT LIPOSITS Basics of Neurobiology: Developmentof thenervoussystem 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 www.itk.ppke.hu FEATURES OF HUMAN DEVELOPMENT FROM THE GAMETES TO THE NEWBORN INDIVIDUAL: THROUGH EMBRYONIC AND FETAL LIFE THE DEVELOPMENTAL SCHEDULE OF THE HUMAN BEING FORMATION OF THE GERM DISCS: THE BILAMINARAND TRILAMINARSTAGES THE MAIN GERM LAYERS PROVIDING THE BASIC TISSUES AND ORGANS OF THE BODY: THE ECTODERM, THE MESODERM AND THE ENDODERM THE DERIVATIVES OF THE THREE GERM LAYERS OF THE EMBRYO THE SIMULTANEOUS DEVELOPMENT OF ORGAN SYSTEMS VULNERABLE STAGES OF THE DEVELOPMENT GENETIC REASONS OF MALFORMATIONS ENVIRONMENTAL REASONS OF DEVELOPMENTAL DEFECTS, EPIGENETICS Basics of Neurobiology: Developmentof thenervoussystem 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 www.itk.ppke.hu THE EARLY EVENTS OF NEURAL DEVELOPMENT FORMATION OF THE NEURAL TUBE FROM THE ECTODERM. THE INDUCTIVE ROLE OF THE NOTOCHORD THE SONIC HEDGEHOG MORPHOGENSIGNALING ANTERIOR AND POSTERIOR NEUROPORESAND THEIR CLOSURE. MALFORMATIONS DEVELOPMENT OF THE NEURAL CREST AND ITS DERIVATIVES FORMATION OF SENSORY AND AUTONOMIC GANGLIA. CONNECTIONS WITH THE CENTRAL NERVOUS SYSTEM AND TARGET STRUCTURES. THE PLACODEPLATE AND ITS DERIVATIVES THE NON-PROPORTIONAL DEVELOPMENT OF THE NEURAL TUBE THE EARLY FORMATION OF THE SPINAL CORD THE EARLY APPEARANCE OF THE BRAIN PRIMORDIUM Basics of Neurobiology: Development of the nervous system 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 www.itk.ppke.hu CELLULAR DIFFERENTIATION OF THE NEURAL TUBE PARALLEL TO THE GROWTH OF THE EMBRYO THE NEURAL TUBE GETS THICKER AND ELONGATES THE CRANIAL END OF THE NEURAL TUBE DEVELOPS MORE INTENSELY RESULTING IN THE PRIMARY BRAIN VESICLES FROM THE LESS INTENSELY PROLIFERATING CAUDAL PART OF THE NEURAL TUBE THESPINAL CORD DERIVES THE EPITHELIAL CELLS LINING THE NEURAL TUBE DIVIDE HEAVILY AND GIVE RISE TO THE CELLULAR CONSTITUENTS OF THE BRAIN AND SPINAL CORD AT FIRST GLIOBLAST AND NEUROBLAST CELLS DEVELOP GLIOBLASTS DIFFERENTIATE INTO GLIAL CELLS THAT MAINTAIN THE SELF-RENEWAL CAPABILITY AND ACCORDINGLY DIVIDE FREQUENTLY IN ADDITION TO PROVIDING ASTROCYTES, OLIGODENDROGLIA AND EPENDYMAL CELLS, GLIOBLAST ALSO FORM RADIAL GLIA CELLS Basics of Neurobiology: Developmentof thenervoussystem 8/5/2011. TÁMOP–4.1.2-08/2/A/KMR-2009-0006 6 www.itk.ppke.hu THE PROCESSES OF RADIAL GLIACELLS STRETCH THROUGH THE ENTIRE THICKNESS OF THE DEVELOPING NEURAL TUBE IN A PERPENDICULAR ORIENTATION RELATIVE TO THE EPENDYMALLINING OF THE NEURAL TUBE RADIAL GLIACELL PROCESSES PROVIDE PATHWAYS AND GUIDANCE FOR NEURONS MIGRATING FROM THE EPENDYMALTO THE MANTLE LAYER THE MIGRATING NEURONS ARE POSTMITOTICCELLS INCAPABLE OF DIVIDING THIS MIGRATORY PROCESS IS CALLED: RADIAL MIGRATION LAYERS GROWING AROUND THE NEURAL CANAL INCLUDE: 1. EPENDYMALLAYER 2. MANTLE LAYER. FORMS THE GREY MATTER 3. MARGINAL LAYER. FORMS THE WHITE MATTER CELLULAR DIFFERENTIATION OF THE NEURAL TUBE Basics of Neurobiology: Developmentof thenervoussystem 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 www.itk.ppke.hu DEVELOPMENT OF THE SPINAL CORD WITHIN THE FOURTH EMBRYONIC WEEK, THE MANTLE LAYER DIFFERENTIATES INTO VENTRALLY LOCATED BASAL AND DORSALLY POSITIONED ALAR PLATES ONBOTH SIDES IN THE MEDIAN SAGITTAL PLANE, THE MANTLE LAYER REMAINS THIN FORMING THE FLOOR PLATE VENTRALLY AND THE ROOF PLATE DORSALLY FROM THE BASAL PLATE THE VENTRAL HORN OF SPINAL CORD DEVELOPS THE DORSAL, SENSORY HORN DERIVES FROM THE ALAR PLATE SOMATO-MOTOR NEURONS DEVELOPING IN THE BASAL PLATE GROW AXONS THAT LEAVE THE SPINAL PRIMORDIUM AND ESTABLISH CONNECTIONS WITH STRIATED MUSCLES DEVELOPING IN THE SAME SEGMENT. THIS IS THE EARLY FORMATION OF THE NEUROMUSCULAR JUNCTIONS VEGETATIVE MOTOR NEURONS DEVELOPING AT THE LEVEL OF THE SULCUS LIMITANS PROVIDE AXONS THAT COMMUNICATE WITH AUTONOMIC GANGLION CELLS OUTSIDE THE SPINAL PRIMORDIUM Basics of Neurobiology: Development of the nervous system RECEPTOR 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 www.itk.ppke.hu NEURONS OF THE ALAR PLATE DIFFERENTIATE FURTHER AND ESTABLISH COMPLEX NUCLEI THAT ARE FUNCTIONALLY COUPLED TO THE PROCESSING OF SENSORY INFORMATION THE SENSORY STIMULI ARE CARRIED TO THE ALAR PLATE BY THE CENTRALPROCESSES OF EXTERNAL PSEUDO-UNIPOLAR NEURONS. THESE CELLS DIFFERENTIATE FROM THE NEURAL CREST AND ESTABLISH THE SENSORY DORSAL ROOT GANGLIA IN THE SEGMENTS OF THE BODY. THE PERIPHERAL PROCESSES OF THESE SENSORY NEURONS ARE LINKED WITH RECEPTORS IN THE MARGINAL LAYER, AXON BUNDLES CAN BE FOUND. THEY EITHER BELONG TO SHORT INTERSEGMENTAL CONNECTIONS OR TO MAJOR ASCENDING AND DESCENDING FIBER TRACTS INTERCONNECTING THE SPINAL SEGMENTS WITHOTHER REGULATORY PARTS OF THE NEUROAXIS DEVELOPMENT OF THE SPINAL CORD ROOF PLATE ALAR PLATE BASAL PLATE FLOOR PLATE STRIATED MUSCLE Basics of Neurobiology: Development of the nervous system 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 www.itk.ppke.hu DEVELOPMENT OF THE BRAIN. FORMATION OF PRIMARY AND SECONDARY BRAIN VESICLES FROM THE ROSTRAL PART OF THE NEURAL TUBE THREE BRAIN VESICLES DERIVE: THE PROSENCEPHALIC, THE MESENCEPHALIC AND THE RHOMBENCEPHLIC VESICLES FURTHER DIFFERENTIATION DIVIDES THE PROSENCEPHALON IN TWO SECONDARY BRAIN VESICLES: THE TELENCEPHALIC AND THE DIENCEPHALIC ONES THE MESENCEPHALIC VESICLE MAINTAINS ITS ORIGINAL INTEGRITY WITHOUT SPLITTING INTO PARTS THE DEVELOPMENT OF THE RHOMBENCEPHALIC VESICLE RESULTS IN THE FORMATION OF THE SECONDARY METENCEPHALIC AND MYELENCEPHALIC VESICLES FORM THE ORIGINAL CAVITY OF THE PROSENCEPHALON THE LATERAL AND THIRD VENTRICLES, FROM THE CAVITY OF THE MESENCEPHALON THE CEREBRAL AQUE-DUCT AND FROM THAT OF THE RHOMBENCEPHALON THE FOURTH CEREBRAL VENTRICLE DEVELOP AT THE LEVEL OF THE 4THVENTRICLE, THREE APERTURES DEVELOP THAT ALLOW THE OUTFLOW OF THE CEREBROSPINAL FLUID INTO THE SUBARACHNOID SPACE Basics of Neurobiology: Development of the nervous system 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 www.itk.ppke.hu SCHEMATIC ILLUSTRATION OF BRAIN VESICLES AND THEIR DERIVATIVES PROSENCEPHALIC VESICLE RHOMBENCEPHALIC VESICLE MESENCEPHALIC VESICLE TELENCEPHALON DIENCEPHALON MESENCEPHALON MYELENCEPHALON METENCEPHALON I. II. III. CA. IV. CEREBRAL CORTEX BASAL GANGLIA THALAMUS HYPOTHALAMUS RETINA MESENCEPHALON PONS CEREBELLUM MEDULLA Basics of Neurobiology: Development of the nervous system 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 www.itk.ppke.hu FOLDING OF THE BRAIN, COMPARTMENTALIZATION OF THE BRAIN STEM THE EMBRYO DISPLAYS A CHARACTERISTIC ROSTRO-CAUDAL, C-SHAPED FLEXURE AT THE END OF THE FIRST MONTH, TWO FLEXURES OF THE BRAIN ARE OBVIOUS. THE CERVICAL FLEXURE OCCURS BETWEEN THE SPINAL CORD AND THE MEDULLA, THE MESENCEPHALIC FLEXURE DEVELOPS AT THE LEVEL OF THE MIDBRAIN.THE CONCAVITY OF BOTH FLEXURES POINTS TOWARD THE VENTRAL PART OF THE BODY LATER, A THIRD FLEXURE DEVELOPS AT THE LEVEL OF THE RHOMBENCEPHALON, CALLED THE PONTINE FLEXURE. IT FOLDS THE METENCEPHALON BACK TO THE MYELENCEPHALON. THE RHOMBIC LIPS THE LATERAL OUT-POCKETINGSOF THE TELENCEPHALICVESICLES ARE ALSO CHARACTERISTIC FEATURES, TOGETHER WITH THE DEVELOPMENT OF THE OPTIC CUP WHICH PROVIDES THE PRIMORDIUM OF THE RETINA THE BRAIN STEM SHOWS AN ORGANIZATION RESEMBLING THE PATTERN OF THE SPINAL CORD. FROM THE BASAL AND ALAR PLATES CENTERS OF CERTAIN CRANIAL NERVES DEVELOP Basics of Neurobiology: Development of the nervous system 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 www.itk.ppke.hu DEVELOPMENT OF THE TELENCEPHALON THE TELENCEPHALIC VESICLES GROW LATERALLY AS BUBBLES ON BOTH SIDES, IN A SPIRAL MANNER SIMILAR TO THE SHAPE OF THE RAM’SHORN. THE DEVELOPING VESICLE PROVIDES THE FRONTAL, PARIETAL, TEMPORAL AND OCCIPITAL LOBES, AS WELL AS, THE INSULA. THESE PARTS GRADUALLY COVER AND HIDE THE DIENCEPHA-LON. THE CAVITY OF THE TELENCEPHALICVESICLE IS THE LATERAL VENTRICLE FROM THE DORSAL PART OF THE WALL OF THE GROWING TELENCEPHALIC VESICLE THE CEREBRAL CORTEX DEVELOPS FROM THE THICKER, VENTRAL PART OF THE VESICLE THE CORPUS STRIATUM DEVELOPS THE VENTRAL SURFACE OF THE TELENCEPHALIC VESICLE GETS JUXTAPOSEDTO THE DIENCEPHALICSTRUCTURE, THE THALAMUS. THIS BORDER ZONE IS CROSSED BY AN EXTREMELY MASSIVE AND FUNCTIONALLY CRUCIAL FIBER BUNDLE SYSTEM, THE INTERNAL CAPSULE. IT CONTAINS FIBERS ESTABLISHING COMMUNICATION BETWEEN THE THALAMUS AND THE CEREBRAL CORTEX, AND ALSO MULTIPLE CONNECTIONS AMONG THE CORTEX, THE BRAIN STEM AND THE SPINAL CORD. BOTH ASCENDING AND DESCENDING FIBER TRACTS ARE REPRESENTED IN IT Basics of Neurobiology: Development of the nervous system 8/5/2011. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 13 www.itk.ppke.hu THE CYTO-DIFFERENTIATION OF THE CEREBRAL CORTEX VZ VZ MZ VZ MZ IZ VZ MZ IZ CP MZ IZ CP SP SV VZ SV ML NC WM VZ SV VZ: VENTRICULAR ZONE MZ: MARGINAL ZONE IZ: INTERMEDIATE ZONE CP: CORTICAL PLATE SZ: SUBVENTRICULARZONE SP: SUBPLATEZONE EL: EPENDYMALLAYER WM: WHITE MATTER NC: NEOCORTEX ML: MOLECULAR LAYER