electrical axon guidance

Question 1

how is an EF generated in tissues?

Answer 1

skin is battery (frogs)

epithelial cell has sodium channel on apical side out to pond water which brings sodium in, and Na/K/ATPase which pumps sodium into tissues

tight junctions between cells stop Na leaking out

more positive inside that pond water

if there is a wound will have localises leaks which induces EF just underneath epithelial layer

Question 2

Electrical signalling regulated neural induction

Answer 2

H+ efflux is greatest at dorsal side gastrula stage

Question 3

how does V-ATPase inhibition impact neural development

Answer 3

embryo not compete gastrulation
downregulates Zic3 - therefore H+ efflux impacts gene expression
loss Zic3 linked to spina bifida in mice
prevents Wnt signalling –> prevents normal neural induction events

Question 4

EFs effects on neural stem cells

Answer 4

EFs can drive
- primary neural induction events
- neural stem cell positioning
- neural stem cell differentiation into neurons

Question 5

proposed cellular mechanism of how growth cones read EFs

Answer 5

voltage gated Ca2+ channels –> increase Ca2+ –> increase cAMP signalling –> RhoGTPase signalling

Rho activity high anodally
Cdc42 and rac activity high cathodally

opposing gradients and mutual antagonism stabilise and amplify gradient across growth cone

Question 6

anandamide and growth cone response to EF

Answer 6

AEA binds to cannaboid 1 receptor, elevating Rho

swamps out gradients , and all parts of growth cone now receiving same Rho signal