MECHANISMS OF AXON GUIDANCE 2 AND 3 Flashcards
POLARITY IS ESTABLISHED AS NEURONS ARE …….
BORN
……… IN ENVIRONMENT INFLUENCE NEURITE SLECTION
CUES
WHAT REGIONS MAKE UP THE ANATOMY OF A GROWTH CONE
CENTRAL
TRANS
PERIPHERAL
THE CENTRAL REGION OF A GROWTH CONE IS MADE UP OF
MICROTUBULES
THE TRANS AND PERIPHERAL REGIONS ARE MADE UP OF
F ACTIN
WHAT IS A FILOPODIA
MEMBRANE PROJECTIONS THAT EXTEND OUTWARDS FROM THE GROWTH CONE
WHAT IS A LAMELLOPODIA
AN ACTIN MESH BETWEEN THE FILOPODIA
IN FILOPODIA THE ACTIN BUNDLES ARE ………………………… TO FORM LARGER ……………….OF NARROW EXTENSIONS
POLARISED
BUNDLES
IN LAMELLA THE ……………. BUNDLES ARE ……………. LINKED INTO A NET.
ACTIN
CROSS
F ACTIN…………………….. IN A RESTING GROWTH CONE
TREADMILLS
WHAT IS TREADMILLING
F ACTIN MOVES FROM THE PERIPHERY TO CENTRE WHERE IT BREAKS DOWN TO REJOIN THE TIP
IN THE RESTING GROWTH CONE, TUBULIN IS DRAGGED SPORADICALLY INTO THE ……………………… - WHEN THE …………………. CONE COMES INTO CONTACT WITH AN ATTRACTIVE ………….., THIS BECOMES MORE ………………
FILOPODIA
GROWTH
CUE
THE GROWTH CONE ……………….. IN THE PRESENCE OF A CUE
REORGANISES
HOW DOES THE GROWTH CONE REORGANISE IN THE PRESENCE OF A CUE
- F ACTIN TREADMILLING SLOWS AND ACCUMULATES
2. ACCUMULATION STABILISES THE FILOPODIUM AND DRAGS MICROTUBULES INTO THE BACK OF THE FILOPODIUM
WHAT CAN AN ATTRACTIVE CUE BE COMPARED TO
ACTS AS A MOLECULAR CLUTCH IN ORDER TO PROPEL THE GROWTH CONE FORWARD
AN …………-TUBULIN LINK PULLS MICROTUBULES IN THE WAKE OF THE EXTENDING FILOPODIA
ACTIN
GROWTH CONES CAN BE ……………………… AND ……………………. BY CUES
REPELLED
ATTRACTED
WHAT STRUCTURALLY HAPPENS TO THE GROWTH CONE UPON REPULSION BY A CUE
THE GROWTH CONE COLLAPSES
THERE IS A DECREASE IN F ACTIN
WHEN MIXTURES OF DIFFERENT NEURONAL TYPES ARE IN CULTURE, WITH WHAT NEURONAL TYPES THEY SEEM TO FASCICULATE WITH
THEIR OWN KIND
WHAT ARE SEMAPHORINS
A FAMILY OF INHIBITORY GUIDANCE CUES
WHAT ARE THE MAIN TYPES OF SEMAPHORINS FOUND IN THE GRASSHOPPER EMBRYO LIMB
MEMBRANE BOUND
WHAT HAPPENS TO THE AXONS OF MICE THAT LACK SEMA3
AXONS STRAY INTO THE WRONG TERRITORIES
WHAT IS THE FUNCTION OF SEMAPHORINS
CAN CHANNEL AXON GROWTH
ALTHOUGH SEMAPHORINS CHANNEL AXON GROWTH WHAT IS STILL ALSO NEEDED FOR AXONAL GROWTH
PERMISSIVE FACTORS
AXON CANNOT ……………… WHERE THEY CANNOT ……………………
BUT THERE IS NO LINK BETWEEN STRENGTH OF ………………………. AND AMOUNT OF AXON GROWTH
GROW
ATTACH
ADHESION
HOW CAN YOU MEASURE ADHESION
WHAT SPEED OF CENTRIFUGE IT WITH DETACH
THERE IS NO LINK BETWEEN STRENGTH OF ADHESION AND AMOUNT OF AXON GROWTH - GIVE AN EXAMPLE
COLLAGEN HAS HIGHER ADHESION BUT LAMININ HAS HIGHER OUTGROWTH
‘COLLAGEN HAS HIGHER ADHESION BUT LAMININ HAS HIGHER OUTGROWTH’
WHAT CAN YOU CONCLUDE FROM THIS
GROWTH CONES NEED SUBSTRATES PERMISSIVE FOR GROWTH, ATTACHMENT IS NOT ENOUGH
EVEN IF A GROWTH CONE IS ………………., IT STILL ATTACHES TO A REPELLANT AXON
REPELLED
PERMISSIVE FACTORS CAN ………………. SUBSTRATE PATHS IN THE EMBRYO. LAMININ PROMOTES GROWTH IN THE OPTIC NERVE BUT IT DOES NOT …………………. THE …………………….. OF GROWTH, ONLY THAT IS CAN ………………. THERE
DEFINE
DICTATE
DIRECTION
GROW
WHAT EFFECT DOES BLOCKAGE OF A LAMININ RECEPTOR DO
SLOWS GROWTH BUT DOES NOT CHANGE THE DIRECTION
………………. OF LAMININ ALSO DO NOT DIRECT AXON GROWTH. IN THIS WAY LAMININ IS ……………………. BUT NOT …………………………
GRADIENTS
PERMISSIVE
INSTRUCTIVE
AXON GROWTH IS A BALANCE BETWEEN PERMISSIVE (CONTACT …………..) AND ……… …………………….(CONTACT REPELLANTS) HOWEVER DIRECTION IS SIGNALLED BY ………………….. ATTRACTION/REPULSION
ATTRACTION
NON PERMISSIVE
CHEMO
WHAT ARE EPHRINS
NON PERMISSIVE FACTORS USED IN EARLY PATTERNING AND TO GUIDE AXONS
EPHRINS ARE CELL …………………. MOLECULES DETECTED BY ……………
THESE CAUSE …………………. BETWEEN CELLS WHICH HELPS TO ……………………………. DISCRETE DOMAINS. LATER IN DEVELOPMENT THEY ARE USE TO KEEP …………….. OUT OF SPECIFIC AREAS.
SUFACE EPHS REPULSION COMPARTMENTALISE AXONA
KEY PATTERNING …………………. SECRETE LONG DISTANCE ………………… MOLECULES CHEMO ATTRACTANTS AND REPELLANTS
ORGANISERS
GUIDING
IF YOU TAKE A DORSAL SPINAL CORD (FLOOR PLATE) EXPLANT AND PLACE IT ECTOPICALLY, AXONS MOVE TOWARDS THE FLOOR PLATE
WHAT DOES THIS SUGGEST
SUGGESTS THERE IS A CHEMOATTRACTANT IN THE FLOOR PLATE
CELL (SUCH AS THE FLOOR PLATE) EXPRESSING THE ……………….. GENE CAN TUEN COMMISSURAL AXONS
NETRIN
WHAT PROTEINS IN THE FLOOR PLATE CAN REPEL COMMISSURAL AXONS
BMPS
LONG AND …………… RANGE CUES WORK …………………. TO GUIDE AXONS TO THEIR TARGETS
EG GRASSHOPPER …………
SUGGESTS A GRADIENT OF SEMA2 DIRECTS TI1 TOWARDS THE BODY WHILE SEMA 1 STOP AXONS FROM STRAYING
SHORT
TOGETHER
COMMISSURAL AXONS ARE GUIDED BY ……………………….. FACTORS IN THE ROOF PLATE AND ……………….. PLATE, BMP7 AND ……………….. RESPECTIVELY.
CHEMOTROPIC
FLOOR
NETRIN
BMP7 IS EARLIER USED TO …………………… THE CELL TYPES OF THE ……………… CORD, ANTAGONISING …………..
THIS SUGGESTS FACTORS MAY BE RE USED FOR ………………. GUIDANCE
PATTERN
SPINAL
SONIC HEADGEHOG
AXON
WHAT HAPPENS WHEN NETRIN IS KNOCKED OUT
AXON GUIDANCE IS DISRUPTED BUT SOME C AXONS STILL MAKE IT TO THEIR DESTINATION
WHY DO SOME AXONS STILL REACH THEIR TARGET IS NETRIN HAS BEEN KNOCKED OUT
BECAUSE SONIC HEDGEHOG ALSO GUIDES AXONS
WHAT WILL A SMOOTHENED KNOCK OUT HAVE AFFECT ON
SMOOTHENED IS PART OF THE SHH PATHWAY
THEREFORE THIS WILL DISRUPT AXON GUIDANCE
HOW CAN YOU GET TISSUE SPECIFIC DELETION OF A GENE
USE OF CRE RECOMBINASE AND LOX P
EXPLAIN METHODOLOGY OF TISSUE SPECIFIC DELETION OF A GENE
- BACTERIOPHAGE P1 ENCODES CRE RECOMBINASE THAT CAN BE INSERTED INTO HOST GENOME
- CRE RECOMBINASE BINDS TO LOXP (A SPECIFIC 34 BASE SEQUENCE) WHICH IS CAN CUT AND BIND TO ANOTHER LOXP
- WE CAN SPECIFICALLY DELETE DNA BETWEEN THESE SEQUENCES - FLOXING
- HOMOLOGOUS RECOMBINATION - CROSSING A MOUSE WITH A FLOXED ALLEL AND A MOUSE WITH A CRE UNDER A TISSUE SPECIFIC PROMOTER WILL GIVE A MOUSE WITH NORMAL EXPRESSION EXCEPT FOR IN THE TARGET TISSUE
AXONS REPROGRAM WHEN ………………… POINTS ARE ENCOUNTERED. AFTER TRANSIT OF THE MIDLINE, C AXONS LOSE ……………………………. TO ……………………..
CHOICE
RESPONSIVENESS
NETRINS
POST CROSSING, AXONS BECOME SENSITIVE TO SOMETHING …………………… IN THE FLOOR PLATE. THERE IS ………………….. OF NETRIN SENSITIVITY AND SENSITIVITY NOW TO ……………………………….. AND SLITS. THESE ARE EXPRESSED IN THE …………………….. PLATE AND ……………….. SPINAL CORD CREATING A CHANNEL THROUGH WHICH C ………………. CAN GROW. THE FLOOR PLATE HAS ………………………………. THE AXONS.
INHIBITORY LOSS SEMAPHORINS FLOOR VENTRAL AXONS REPROGRAMMED
WHAT DETERMINES WHETHER C AXONS CROSS OR NOT AND WHAT PREVENTS RECROSSING
ROBO (ROUNDABOUT)
COMM (COMMISSURELESS)
WHAT IS ROBO
RECEPTOR FOR SLIT
WHAT IS THE ACTION OF ROBO
WHERE ROBO IS EXPRESSED AT HIGH LEVELS ON AXONS THAT DO NOT CROSS THE MIDLINE
WHAT OCCURS IN ROBO MUTANTS
ROBO MUTANTS CANNOT DETECT SLIT AND THEREFORE KEEP CROSSING THE MIDLINE
WHAT IS COMM
COMM IS EXPRESSED ONLY IN AXONS THAT NORMALLY CROSS THE MIDLINE
WHAT HAPPENS TO A COMM MUTANT
AXONS DO NOT CROSS THE MIDLINE AND ARE LONGITUDINAL ONLY
FORCED COMM EXPRESSION RESULTS IN WHAT
A PHENOTYPE THAT MATCHES THE ROBO MUTANT
WHAT CAN BE SAID ABOUT FORCED COMM EXPRESSION IN CONCLUSION
COMM CONTROLS ROBO
HOW DOES COMM CONTROL ROBO
COMM CONTROLS A TRAFFICKING PROTEIN REACHING THE CELL SURGACE TO THAT THE GROWTH CONE CANNOT RECEIVE SLIT INHIBITORY SIGNALS BEFORE CROSSING
COMM AND ROBO ARE NOT FOUND IN VERTEBRATES, WHAT OCCURS IN VERTEBRATES INSTEAD
IN VERTEBRATES ROBO=ROBO1 BUT IT IS EXPRESSED BEFORE AND AFTER CROSSING
THERE IS NO COMM, ONLY ANOTHER ROBO LIKE PROTEIN, RIG 1 THAT APPEARS TO BLOCK ROBO1 UNTIL THE MIDLINE IS CROSSED
FOLLOWER AXONS USE THE ………………….. SCAFFOLD. THEY MUST STAY ON AND GET OFF AT THE RIGHT PLACE. THIS IS DONE BY …………………. BINDING BY CELL ………………….. MOLECULES.
FASCICULATION AND DEFASCICULATION IN FLIES IS CONTROLLED BY ……………………..2. BEAT PROTEIN CAN ALSO CAUSE ……………………..
PIONEER HOMOPHILIC ADHESION FASCICULIN DEFASCICULATION
OVEREXPRESSION OF FASCICULIN 2 CAUSES WHAT
AXONS TO MISS THEIR TARGETS
WHAT ARE THE TWO TYPES OF TARGET SELECTION
DISCRETE (CELLULAR)
TOPOGRAPHIC (MULTICELLULAR)
IN DISCRETE TARGETS, ABLATION OF THE TARGET MUSCLES LEADS TO WHAT
FAILURE OF THE MOTOR AXON TO LEAVE THE TRUNK
THE TARGETS SECRETE CUES THAT PROMPT THE AXONS TO LEAVE THE TRUNK AND DEFASCICULATE TO THEIR TARGET. WHAT ARE EXAMPLES OF THE CUES.
NETRIN
FASCICULIN 3
IN TOPOGRAPHIC MAPS, …………………………… NEURONS SEND ……………… TO NEIGHBOURING SITES TO MAINTAIN ORDER.
NEIGHBOURING
AXONS
THERE ARE TWO THEORIES FOR TARGETS BY SPERRY WHAT ARE THEY
- EACH AXON HAS A SPECIFIC LABEL FOR EACH TARGET
2. A COORDINATE SYSTEM OF GRADIENTS OF SIGNALLING MOLCEULES OF LONGITUDE/LATITUDE READ BY RECEPTORS OF TARGET
WHICH OF SPERRY’S TWO TARGET THEORIES WAS CORRECT
MODEL 2
HOW CAN WE SHOW MODEL 2 TARGET SELECTION THEORY WAS CORRECT
THE STRIPE ASSAY
WHAT IS THE STRIPE ASSAY
CELLS FROM THE POSTERIOR TECTUM MAKE A NON PERMISSIVE FACTOR THAT REPELS TEMPORAL RETINAL AXONS
TEMPORAL AXONS AVOID STRIPES OF THE POSTERIOR TECTUM
WHAT IS THE INHIBITORY FACTOR CAUSING STRIPES IN THE POSTERIOR TECTUM
EPHRINS A2/A5 TO RECEPTOR EPH A3
WHAT CAN WE CONCLUDE ABOUT THE STRIPE ASSAY
NON PERMISSIVE REPELLANT FACTORS CAN BE INSTRUCTIVE TO FORM TOPOGRAPHIC MAPS