wiring of the brain Flashcards
what does neuroregulin 1 do?
important in tangential neurons migration differentiation and survival - these are fast-spiking/paravalbumin interneurons
these are necessary for gamma oscillations
what is ErbB?
receptor of neuroregulin
can form fuctional homodimers
have tyrosine kinase activity
in tangential migration
what do guidepost cells do?
express specific molecules that alter signaling in growth cones and change actin structure to change growth cone direction
critical in development of brain
act as information kiosks - express cues on outside of cells that interact with proteins expressed on axons
growth cones of pioneer neurons contact these stationary cells at intermediary distances in limb bud and at critical change points
what are corridor cells?
guidepost cells for thalamocortical afferents (TCA)
immature GABAergic interneurons
“steer” growth cones of nascent TCAs as they traverse the developing brain
derived from LGE but migrate tangentially into the MGE and form a permissive zone between the MGE and primordial globus pallidus
signaling depends on neuroregulin-1 (expressed on corridor cells) /ErbB4 (expressed on growth cones of TCAs) signaling
what are growth cones?
end of growing axon - have filipodia that sense movement
these are part of the sheet-like lamellipodia
sense and test the environment around them
growth cones of pioneer neurons have active filopodia, follower neurons have less complex growth cones
what are pioneer neurons?
explorers
establish the pathways upon which other neurons subsequently travel to build fascicles
growth cones have many active filipodia
in vertebrates, these are also primary sensory neurons - undergo programed cell death when dorsal root ganglia form and the sensory neurons in the DRG replace the pioneer neurons
what are Rohon-Beard cells?
type of pioneer neurons
undergo programed cell death when dorsal root ganglia form and the sensory neurons in the DRG replace the pioneer neurons
what are trophic factors? what are some examples?
molecules that promote survival and growth
can also be tropic
eg. NGF, BDNF, growth factors
what are tropic factors?
molecules that guide growth
eg. extracellular matrix proteins (ECM) cell adhesion molecules (CAMs) ephrins netrins slit semaphorins neurotrophins and other GF
what are extracellular matrix molecules?
eg laminins collagens and fibronectin
proteins that are expressed extracellularly and create a gelatinous like substance inside the brain - provides structure for cells to bind to and migrate on and also holds and allows for the diffusion of proteins into a gradient
integrins and other proteins on growing cells (and on growth cones) can bind to them, resulting in an intercellular signaling cascade that changes growth, differentiation and migration
what are cell adhesion molecules?
CAMs
come are Ca dependent = cadherins
some are Ca independent = N-CAM and others
include members of IgG superfamily
often axons that express the same CAMs fasciculate
nondiffusable signals for axon growth
if it’s the right kind of axon, will latch on and follow/move towards them
expressed by pioneer and follower axons as well as substrate cells
what are netrins? what does it do? what affects it’s ability to act?
bind to DCC
type of soluble tropic signaling molecule
multifunctional - can both attract and repel, depending on the type of axon/cell
growth cones will turn towards it if the [cAMP] levels are high
if cAMP depleted or PKA inhibited, grows away from netrin gradient
what does slit do? what is it? what is it important for?
type of soluble tropic signaling molecule
binds to robo (roundabout)
expressed by midline floor plate neurons
important in preventing neurons from recrossing the midline - so slit will prevent axons on neurons that are supposed to have their axons in the contralateral hemisphere from coming back to the hemisphere where the cell bodies are
what attracts axons to cross the midline?
slit repels neurons that express robo
netrin attracts the neurons that express DCC
before crossing, commissural axons have low levels of robo1 and high levels of robo3 - robo3 inhibits robo1 signaling - so netrin is active, slit is not - so they are attracted to the midline and cross
after crossing the midline, though, the robo3 levels expressed in these axons decrease, and robo1 levels increase - now repelled by slit
netrin signaling is also altered (by changing PKA levels) so netrin is no longer an attractant
=> the axon stays on that side of the brain
how are maps that guide movement of axons created?
by ephrins and ephs
exist in complementary gradinets in the tectum/superior colliculus (ephrins) and on retinal ganglion cell axons (Eph receptors)
axons with high levels of EphA receptors map to superior collicular cells with lowest levels of ephrinA => temporal/nasal::anterior/posterior positioning
gradients of ephrinB and ephB establish dorsal/ventral map
