Developmental Neurobiology - CNS

Neuroepithelial cell division

Generate radial glia and neuronal precursor

Birth dating with titrated thymine

Thymine is used in new DNA, but only cells that are done dividing retain the label aka neuronal precursors

Early precursor transplant

Adopt the fate of cells born at the time of transplant

Later precursor transplant

Retain their original fate

Lissencephaly

No sulci or gyri, mutation in TUBA1A and TUBB2B because microtubules are needed for migration

Cajal-retizius and subplate cells

Cortical plate forms between them, reelin mutants can’t separate them causing lisencephaly

Adult neural stem cells

Radial glia subset become astrocyte-like

Rhombic lip cells in cerebellum

Anterior go to external germinal layer (granule neurons) and interior go to ventral hindbrain (pontine nuclei)

Resonance theory of connectivity (Weiss)

Random growth to targets and non-useful ones are pruned

Chemoaffinity hypothesis of connectivity (Sperry)

Specific growth to targets

Axon cues

Cues found on axons can tell other axons if they need to stop/turn etc

Pioneer axons

Rely on signals from cells to form a pathway for follower axons to use

Lamella

Actin bundled in a crosslink to form a net

Filopodia

Actin is polarised to form larger bundles

Semaphorin

Inhibitory molecule causing f actin collapse

Permissive substrates

Where growth cones can grow, doesn’t tell them what direction to grow

Ephrins

Detected by Eph and cause repulsion between cells

Netrin

Chemoattractant released by floor plate

BMP

Causes growth cone collapse

Shh

Chemoattractant, blocked by cyclopamine

Slit

Chemorepellant on the midline

Robo

Detects Slit repellant signals

Comm

Blocks Robo until after the axon has crossed the midline

Fasciclin

Helps nerves bundle together and leave at the right point

Beat

Cause defasciculation so nerves get to their targets

Bax/Bcl-2

Anti apoptitic

Caspase 1

Executioner, pro apoptitic

Caspase 9

Initiator, pro apoptitic

NGF

Found in tumours, promotes growth of axons

Neutrophin family

BDNF, NT3/4/5

Nodose ganglion dependence

BDNF/NT 3

Crest derived DRG dependence

NGF, BDNF, NT3

Sympathetics dependence

NT3, NGF

TTX

Tetredotoxin from pufferfish, block Na+ channels