Lecture 8

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Cell and Systems Biology
Melanie Woodin

CSB332H1S L8; Feb. 06, 2012  Axon Guidance Reading = Pg. 550-557  Short answer qs: allowed to be done in point form, spelling of scientific terms matters, don’t contradict self       Growth cone – extending tip growing out of axon o Responsible for sensing envt and navigating o Pulls axons in the dir’n it senses  Arm = axon; hand = growth cone  Axons extend growth cones (specialized sensory structure full  Growth cone under brightfield/standard light (Differential of recs sensing molecular cues in envt to guide in proper dir’n) Interence Contrast DIC) w microscope to find target neurons to form synapses with  2 flurorescent images:  Must form appropriate synapse (inhibitory vs excitatory) o Microtubules extended into filopodia  Once synapse forms, how becomes plastic thru life of adult o Actin filaments mostly inside growth cone  Microtubules also go into growth cone  Actin predominantly in periphery of growth cone  Almost act independently  Lamellipodia = broad spatula-like ending, like palm of hand o If have growth cone growing & sever axon  growth cone  Filopodia = microspikes that come out of lamellipodia, like continues fn’ally for 24hrs looking for attractive cues fingers o Proximal region still has organelles – mitochondria,  Both are rich in actin vesicles to recycle membrane – working w/o cell body  Actin can continually polymerize to direct growth of growth o So can act almost iindependently cone  Filopodia adheres & positively pulls axon o Very dynamic, constantly extending tips to sample envt o Can sense things as attractive or repulsive (pulls growth cone to go in opposite direction or to retract)  Retina axons  Lateral geniculate nucleus  visual cortex  Axons from LGN (red) eventually want to get into cortical plate, but can’t go directly o Grow to bases of cortical plate, called subplate  By this time, neurons in visual cortex haven’t been  Stationary: sampling envt but not moving back & forth born yet o Actin not anchored to anything  So LGN axons form transient synapses with neuronss  Protrusive: growing forward in subplate, wait until neurons born in layer 4 of o Actin filament had immobilized to substrate  actin visual cortex (ultimate location of synapses)   abandon subplate synapses becomes anchored o  growth cone moves forward   go directly from LGN to cortical plate  Green actin filament constantly being polymerized at front &  Modifications of guidepost cells o If guidepost cell very prominent, growth cone forms depolymerized at back – constat recycling  Actin filament in contact w microtubule via myosin (powering synapse with it and waits til appropriate time movement of actin) anchored to microtubule   Read in book about cohesion molecules & extracellular matrix molecs – bind directrtly to recs to anchor to neurites  Axon in spinal must cross base of spinal cord and exit on opposite side of body  Axon gets attracted to region where crosses over, then repulses by midline so keeps going  Can sense chemoattracts (diffused)  Commissural interneuron in dorsal region, grow ventrally to  Tactics depends on distance needed to grow developing part of ventral spinal cord to floor plate cells – have specilialized cells releaseing chemoattractants & repellants  Ex. chemoattract released out of toe: unlikely to diffuse all the way up spinal cord  Interneuron expresses DCC rec (don’t need to know long-form)  Guidepost cells located along route – neuron must locate each  Foreplate releases longrange chemoattract, gradient highest at floorplate – attracts DCC rec guidecell (like points on google maps)  Ti1 normally looks for F1, then F2, then CT1  When get close to source of chemoattractant  difficulty o If remove CT1: can’t find CT1, sends out original growth sensing dir’n since concentration of chemosattratant high  Direct binding btwn NrCAM to TAG-1 rec of growth cone cone projections looking for guidepost cells  Rarely will find correct path
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