Key
intracellular
secreted proteins
membrane-bound
parts
protein receptors
Relationships
Blocks, repels
Activates, attracts
Reciprocal Gradient
Floor Plate
Notochord
Ectoderm
Roof Plate
Sensory Neurons
Motor Neurons
Commisural Neurons (Pre-Commisural)
Commisural Neurons (Post-Commisural)
To Brain
Cadherins
Ca2+ based cell-adhesion proteins
Many types
Cells connect homophillically -> attach to others with the same type Cadherin expression
Different types for regional separation
Beta-Catenin
when overexpressed, forms a much larger brain
unknown details, suggested that it elongates proliferative period
Early Polarity
SHH
Sonic Hedgehog
Secreted by Notochord
induces formation of Floor Plate
Secreted by Floor Plate
induces formation of Motor Neurons
BMP
During Gastrulation
Bone Morphogenic Protein 4
Secreted by most cells
Receptors activated by BMP-4 fate cells to become epidermal
Post Gastrulation
Released from Neural Crest
Induces formation of Roof Plate
Released from Roof Plate
Induces formation of Sensory Neurons
Noggin
Expressed at gastrulation
Expressed by mesodermic cells
Prevents binding of BMP-4
Allows cells to follow natural fate -> to become neurons
Proliferation
Notch1
At alar pole of cell
allows cell to travel away from mitotic phase
Numb
At basal pole of cell
keeps cell bound to ventricular floor
keeps cell in mitotic phase
Horizontal vs. Vertical Cleavage determines which is active
Migration
Reelin
Secreted by Cajal-Retzius cells
first cells present, before neurogenesis
Causes migrating neuroblasts to migrate past
allows for inside-out neurogenesis
Prokineticin
Attractant
Released by Olfactory Bulb
Slit-Netrin
Slit
Repellant
Secreted by Septum
repels Olfactory cells migrating towards Bulb
repels Mitral cell growth cones from Bulb
Floor Plate
Released locally
Induces movement of Commisural growth cones out of Floor Plate
Robo
Receptor for Slit
Induces growth or movement down Slit gradient
Olfactory Bulb
Expressed in Granule Cells migrating to Olfactory Bulb
Expressed in Mitral cell Growth Cones coming from Olfactory Bulb
Floor Plate
Activated in Commisural Growth Cones
dimerizes with DCC until DCC is saturated
DCC
Dimerizing receptor for Netrin
Induces growth cone to grow up Netrin gradient
deactivated by dimerization with Robo
Netrin
Attractant
under normal situations
At Floor Plate
Attracts Commisural Neurons
Repellant
under altered cAMP levels
wnt4
Gradient Increasing up brainstem to brain
attractant
post-commisural neurons follow this
pre-commisural are immune
fz3
Disorients neurons
Semaphorins
Chemorepellant
Causes collapse of Philapodia & Lamellopodia
Oligodendrocytes & Myelin
Repellant
On contact, growth cones collapse & retreat
Astrotactin
Created by neuroblasts
induces adhesion to Radial Glial Processes
Extra Cellular Matrix
Laminin & Fibronectin
In Cerebellum
Released to help migration of Granule cells from IVth ventrical to Pial surface
Only found in E.C.M.
Neural Crest
Neural crest follows gradient to form Spinal Ganglia
Integrin
Expressed in Granule cells at Cerebellum
Migration from IVth Ventrical @ Subventricular Layer to Pial Surface
CSPG's
Chondroitin Sulfate Proteoglycans
repellant
Optic Development
Initially fills whole Optic Cup except nerve head
Induces movement of axons towards nerve head
Also at more dorsal regions of optic tract
creates chronotopic organization b/c new growth cones are repelled towards ventral end
Ephrins
EphA
Receptor for EphrinA
Repelled
Temporal (+) - Nasal (-) gradient in Retina
Rostral (+) - Caudal (-) gradient in Thalamus
EphrinA
Secreted in Tectum
Repellant
Caudal (+) - Rostral (-) gradient in Tectum
Caudal (+) - Rostral (-) gradient in Striatum
Partial Decussation @ Optic Chiasm
Ephrin B2
High levels in chiasm
Repellant
EphB1
Receptor for Ephrin B
Induces repulsion -> sends axons ipsilateral
Zic2
Activates EphB1
Islet2
Deactivates Zic2 and EphB1
Induces contralateral growth