Brain development
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| CNS origins | Neural tube -> midline ectoderm dorsal to notochord specified to form neural tissue -> invaginates to form neural tube w/ neural plate region -> plate folding (neurulation) -> forms closed neural tube (spinal cord)
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| Neural tube defects | Spina bifida occulta -> small gap in spine but no dorsal opening/sac
Myelomeningocele -> dorsal sac of fluid containing damaged spinal cord/nerves
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| PNS origins | Neural tube closure -> NCCs emigrate from dorsal neural tube to embryo
Neurogenic placodes -> neurons delaminate from placode and migrate inside embryo -> coalesce w/ NCC-derived glia to form ganglia
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| What neurons do cranial NCCs form? | Invade pharyngeal arches/surround brain -> somatosensory neurons, cranial sensory ganglia, parasympathetic ganglia (ciliary III, pterygopalatine/submanidbular VII, otic IX), terminal parasympathetic ganglia X
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| What neurons do vagal NCCs form? | Caudal hindbrain -> invade heart/gut -> enteric neurons/glia
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| What neurons do trunk NCCs form? | DR neurons/glia and sympathetic ganglia
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| Axon growth cone | Actin/myosin interactions promote neuron motility -> moves towards suitable adhesive substrate -> regulated via adhesion and signalling
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| Axon scaffolds | Embryonic neuroepithelium, mechanical cues
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| Diffusible attractive molecules | Long range chemoattraction -> nerve growth factor (NGF) such as netrin
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| What does neurotrophic mean? | Nourishing -> promotes neuron survival/sprouting (NGF)
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| What does neurotropic mean? | Attractive -> growth cone chemotaxis -> promotes neuron directional growth
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| Diffusible repellant molecules | Long range chemorepulsion -> secreted semaphorins -> slit chemorepulsion
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| Contact repulsion molecules | Short range -> Eph ligands, transmembrane semaphorins, ECM (tenascins)
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| Contact adhesion molecules | Short range -> Ig CAMs, cadherins, ECM (laminin)
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| CAMs | Connect to growth cone cytoskeleton and signal transducers
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| What is the optic tectum? | Midbrain roof
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| Retinal axon growth to tectum | Retinal ganglion cell axons cross the midline -> navigate to optic tectum by following local guidance cues in neuroepithelium rather than diffusible signals released from target
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| Mechanical cues for axon growth | Axon grows towards softer tissue in vitro/vivo -> stiffness = high cell density
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| Retinotectal projection | Temporal retina -> contralateral anterior tectum
Nasal retina -> contralateral posterior tectum
Dorsal retina -> contralateral ventral tectum
Ventral retina -> contralateral dorsal tectum
Rely on counter gradients of ephrin/Eph in retina/tectum
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| Synapse formation in vitro | Promiscuous formation
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| Synapse formation in vivo | Axon guidance via NGF, ephrin, CAMs -> generic synapse formation via synapse specific adhesion molecules -> acitivty dependent selection (LTP stabilisation)
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| Ephrins in tectum | EphrinA in posterior tectum repels EphA axons from temporal retina
EphrinB in ventral tectum attracts EphB axons from nasal retina
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