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Brain development

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)
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
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
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
What neurons do vagal NCCs form? Caudal hindbrain -> invade heart/gut -> enteric neurons/glia
What neurons do trunk NCCs form? DR neurons/glia and sympathetic ganglia
Axon growth cone Actin/myosin interactions promote neuron motility -> moves towards suitable adhesive substrate -> regulated via adhesion and signalling
Axon scaffolds Embryonic neuroepithelium, mechanical cues
Diffusible attractive molecules Long range chemoattraction -> nerve growth factor (NGF) such as netrin
What does neurotrophic mean? Nourishing -> promotes neuron survival/sprouting (NGF)
What does neurotropic mean? Attractive -> growth cone chemotaxis -> promotes neuron directional growth
Diffusible repellant molecules Long range chemorepulsion -> secreted semaphorins -> slit chemorepulsion
Contact repulsion molecules Short range -> Eph ligands, transmembrane semaphorins, ECM (tenascins)
Contact adhesion molecules Short range -> Ig CAMs, cadherins, ECM (laminin)
CAMs Connect to growth cone cytoskeleton and signal transducers
What is the optic tectum? Midbrain roof
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
Mechanical cues for axon growth Axon grows towards softer tissue in vitro/vivo -> stiffness = high cell density
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
Synapse formation in vitro Promiscuous formation
Synapse formation in vivo Axon guidance via NGF, ephrin, CAMs -> generic synapse formation via synapse specific adhesion molecules -> acitivty dependent selection (LTP stabilisation)
Ephrins in tectum EphrinA in posterior tectum repels EphA axons from temporal retina EphrinB in ventral tectum attracts EphB axons from nasal retina
Created by: vykleung
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