Lecture 21 - Shelly

Lecture 21 - Shelly - 11/16/2011 Early Signaling Events in...

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11/16/2011 1 Early Signaling Events in the Establishment of Axon/Dendrite Polarity During Neuronal Development Maya Shelly E.mail: maya.shelly@stonybrook.edu Office Location: Room 530, Life Science Bldg. Office Hours: Tuesday, 12:30 PM - 1:30 PM November, 2011 Early Signaling Events in the Establishment of Axon/Dendrite Polarity During Neuronal Development * The Mature Neuronal cell Exhibits a Polarized Structure of Axon and Dendrites: --Cortical neurons in the embryonic brain, --Cultured dissociated hippocampal neurons in culture . Principles of Neuronal Symmetry breaking . * Examples of Polarized Cells: Conservation of Polarization Signaling Mechanisms in different cell types and throughout evolutionary distant species: --PAR family of proteins. * Axon Initiation vs. Axon Elongation and Growth, * Is the Axon Fate Pre-Determined or can any Neurite Be an Axon? --Is the Axon fate modifiable ? * Molecular Signaling Mechanisms of Axon Initiation: -- cAMP/PKA Signaling for axon initiation, -- LKB1 Serine/Threonine Kinase – an essential early factor for axon initiation, -- Antagonism between cAMP/cGMP signaling pathways.
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11/16/2011 2 The Mature Neuronal cell Exhibits a Polarized Structure of Axon and Dendrites Embryonic Rat Cortical Axon and Dendrites Differ: 1. Morphology, 2. Molecular composition, 3. Function. CP IZ IZ CP VZ Development VZ Age (Days) E12 E18 Embryonic Rat Brain SVZ – Sub-Ventricular Zone IZ – Intermidiate Zone CP –Cortical±Plate How are the processes of axon and dendrite morphogenesis and neuronal migration coordinated in the developing brain? Coordinated Development and Migration of Cortical Progenitors Noctor et al., Nat. Neurosci. (2004). 1. Upon mitosis in the sub-ventricular zone, rapid radial migration to the ventricular zone. 2. Migration arrest at the ventricular zone, and development of neuritic processes. 3. Retrograde Ventricular migration. 4. Polarity reversal (leading/trailing processes), and migration to the cortical plate.
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11/16/2011 3 Dissociated Embryonic Hippocampal Neuron in Culture 12 hr 60 hr 12 hours follwong plating The same cell - 60 hours follwong plating Isolated Neurons in Culture Develop Morphologically and Functionally Distinct Axon/Dendrite Domains Gary banker, 1994: “We know almost nothing about the compartmentation in neurons…” Dissociated Embryonic Hippocampal Neurons in Culture Stage 2 (after 6h) Stage 3 (after 24h) Stage 4 (after 2 3 days) Stage 5 (after 4 days) cytoskeletal protrusions axon formation/growth dendrite formation axon / dendrite maturation neurite initiation Stage 1 (first 6h) axon initiation
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11/16/2011 4 Symmetry Breaking and Neuronal Polarization Radially Migrating Pyramidal Neurons in Mammalian Neocortex Dissociated Embryonic Hippocampal Neurons in Culture Cortical plate Intermediate zone SVZ VZ Stage 2 (after 6h) Stage 3 (after 24h) Stage 4-5 (after 2-3 days) Stage 1 (first 6h) Symmetry Asymmetry cytoskeletal protrusions axon development/growth dendrite formation neurite initiation axon initiation Symmetry Asymmetry Radial glial progenitor Symmetry Breaking… Symmetry Broken Symmetry
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11/16/2011 5
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Lecture 21 - Shelly - 11/16/2011 Early Signaling Events in...

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