of the Max - MDC

Lack of axonal bifurcation within the spinal cord in the absence
of cGMP signalling.
(E) Scheme summarizing the defects observed in the absence of
cGMP signalling. In the left of the panel is indicated the normal
pattern of axonal growth while the right reveals the observed errors.
(F) Scheme on the cGMP signalling pathway in embryonic DRGs: The
receptor guanylyl cyclase Npr2 generates cGMP that might activate
the cGKI which in turn phosphorylates so far unknown proteins.
Scale bar in D, 100µm.
(A) Schematic drawing of the trajectories of sensory axon projections
within the spinal cord. A sensory axon enters the spinal cord at
the dorsal root entry zone, bifurcates and extends in rostral and
caudal directions. These stem axons then generate collaterals that
populate the dorsal or ventral horn of the spinal cord.
Failure of sensory axons to bifurcate in the absence of serine/
threonine kinase cGKI (C) or the receptor guanylyl cyclase Npr2 (D).
(B) shows normal bifurcating axons when cGMP signalling is not
impaired.
molecular analysis of the activity-dependent regulation of
neuronal circuits.
One of our searches led to the identification of the transmembrane
proteins CAR (coxsackie- and adenovirus receptor)
and CALEB (chicken acidic leucine-rich EGF-like domain
containing brain protein) that are regulated by neuronal
activity. While the evidence for CAR to be implicated in
synaptogenesis is at a very early stage there are compelling
results that CALEB regulates pre-synaptic differentiation.
The characteristic feature of CALEB is an EGF-like domain
close to its plasma membrane-spanning region that is related
to TGFα or neuregulin-1. CALEB contains an acidic box
that binds to the extracellular matrix glycoproteins
tenascin-C and -R. CALEB becomes glycosylated by chondroitinsulfate
chains at the N-terminus and is generated in
at least two isoforms that differ in their cytoplasmic region.
CALEB is found throughout the nervous system and displays
a developmentally regulated expression profile in many
Function and Dysfunction of the Nervous System 171