Golan H. 20101 Neural Development. Golan H. 20102 Neural Development 1.General trends in Neurogenesis: Example from the development of the cerebral cortex:

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Presentation transcript:

Golan H Neural Development

Golan H Neural Development 1.General trends in Neurogenesis: Example from the development of the cerebral cortex: Differentiation, Migration, Path finding and Synaptogenesis. 2. Molecular signals and activity dependent signaling: Cell-Cell contact Cell-Matrix contact Binding of diffusible factors (attraction-repulsion) 3. Cell-Cell signal transmission: Electrical and chemical synapses. 4. Genes vs. environment.

Golan H “Vision depends critically on the right number of cells, the right ratio of cell types, and the right distribution of cells across the surface of the retina”. Walls, 1942.

Golan H התפתחות מוחית בעובר מעגלים תפקודיים במוח תנועה ראיה תחושה 100,000,000,000 תאי עצב פי תאי גליה כל תא יוצר כ 10,000 קשרים עם תאים אחרים ( סינפסות )

Golan H First stage: Neurolation Neuronal tube Neuronal plate יצירת הצינור העיצבי – במהלך חודשיים ראשונים להריון

Golan H מהצינור העיצבי מתפתחות 5 שלפוחיות Second stage: Histogenesis

Golan H שלב זה כולל : חלוקת תאים התמיינות נדידה מציאת אתר מטרה לעצבוב על ידי אקסונים יצירת סינפסות ובמקביל – התפתחות עץ דנדריטי תמותת תאים ( התפתחותית )

Golan H בתהליך ההתפתחות מעורבים :  המטען התורשתי  השפעת סביבה השפעת הסביבה נעשית באמצעות : רמזים מולקולריים פעילות חשמלית

Golan H Pia VZ CR : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : Pia : : : : : : : : : : :. :. : : : : : : : : : : : : Cortical development VZ Pia Radial Glia

Golan H Cortical development Cooper, TINS, 2008 Neurons migration

Golan H Cortical development Cooper, TINS, 2008

Golan H Cortical development

Golan H כיצד יודע התא לאן עליו לצמוח ? עם איזה תא עליו ליצור קשר ??

Golan H רמזים מולקולריים המופרשים על - ידי התאים או נמצאים על גבי התאים מכוונים את הצמיחה.

Golan H רמזים מולקולריים שייכים למספר " משפחות של מולקולות ": פקטורים נוירוטרופים מולקולות אדהזיה

Golan H Environmental effect on Progenitor cells: Cell-Cell contact (CAM) Cell-Matrix contact ( Integrins) Binding of diffusible factors to cellular receptors

Golan H

Golan H Contact attractionContact repulsion Chemo-attractionChemo-repulsion

Golan H

Golan H Growth cone filopodia – Axon (presynaptic terminal ) Dendritic filopodia – Dendrite (PSD)

Golan H Neurotrophic Factors determines growth direction Repulsion Attraction Growth cones path finding path finding

Golan H Growth cones path finding path finding

Golan H Chemo-attractionChemo-repulsion תלות במטבוליטים בסביבה : פעילות חשמלית, cAMP, cGMP, Ca קבוצה 1 : מגיבים ל cAMP : Ach, BDNF (trk B), Netrin I, MAG קבוצה 2 : מגיבים ל cGMP : NT-3 (trk C), sema3A, slit

Golan H Goodmand and Tessier-Lavigne, 1996

Golan H Goodmand and Tessier-Lavigne, 1996

Golan H Goodmand and Tessier-Lavigne, 1996

Golan H The Slit ligand and Roundabout (Robo) receptors Ligand/receptor system that contribute to proper conectivity in both the vertebrate and invertebrate nervous systems. Influence neuronal and mesodermal cell migration.

Golan H Cell Dev. Biol :651–75 Figure 2

Golan H Robo & slit

Golan H סיכום - אסטרטגיה של צימוח : צימוח בסגמנטים – saltatory growth נקודות החלטה choice points – צימוח על גבי ראשונים – pioneers and followers רמזים סביבתיים – push and pull

Golan H Neuronal Circuit Establishment Molecular cues Neurothropic factors, adhesion molecules, chemoattractants, Chemorepulsive….. Activity dependent development Spontaneous – network establishments. Evoke- strengthen of functional networks and elimination of unfunctional connections.