Welcome to Zou Lab
The Zou lab at UCSD studies development, function and repair of neural circuits. We are interested in how neurons in the nervous system form highly organized and precise connections to give rise to function. We believe studying neural circuit assembly at molecular and cellular level will reveal fundamental principles of how the complex connections of the entire nervous system are organized. We also study how neural circuits degenerate and how adult central nervous system responds to injury.
Latest News
Dec 4, 2013:
Onishi et al published new findings on signaling
mechanisms that mediates growth cone turning. How growth cones detect
small concentration differences of guidance cues for correct steering
remains a long-standing puzzle. Commissural axons engage planar cell
polarity (PCP) signaling components to turn anteriorly in a Wnt
gradient after midline crossing. We found here that Frizzled3, a Wnt
receptor, undergoes endocytosis via filopodia tips. Wnt5a increases
Frizzled3 endocytosis, which correlates with filopodia elongation. We
discovered an unexpected antagonism between Dishevelleds, which may
function as a signal amplification mechanism in filopodia where PCP
signaling is activated: Dishevelled2 blocks Dishevelled1-induced
Frizzled3 hyperphosphorylation and membrane accumulation. A key
component of apical-basal polarity (A-BP) signaling, aPKC, also
inhibits Dishevelled1-induced Frizzled3 hyperphosphorylation. Celsr3,
another PCP component, is required in commissural neurons for
anterior turning. Frizzled3 hyperphosphorylation is increased in
Celsr3 mutant mice, where PCP signaling is impaired, suggesting
Frizzled3 hyperphosphorylation does correlate with loss of PCP
signaling in vivo. Furthermore, we found that the small GTPase, Arf6,
which is required for Frizzled3 endocytosis, is essential for
Wnt-promoted outgrowth, highlighting the importance of Frizzled3
recycling in PCP signaling in growth cone guidance. In a Wnt5a
gradient, more Frizzled3 endocytosis and activation of atypical
protein kinase C was observed on the side of growth cones facing
higher Wnt5a concentration, suggesting that spatially controlled
Frizzled3 endocytosis is part of the key mechanism for growth cone
steering.
Please click here to download the PDF file.
Oct 7, 2013:
Anna Tury et al published their studies on changes
of Wnt signaling components in an ALS mouse model. Amyotrophic
lateral sclerosis (ALS) is a fatal neurodegenerative disease
characterized by progressive paralysis due to the selective death of
motor neurons of unknown causes. Increasing evidence indicates that
Wnt signaling is altered in ALS. In this study, we focused on two
non-canonical Wnt signaling components, atypical PKC (aPKC) and a Wnt
receptor, Ryk, in a mouse model of ALS, SOD1 (G93A). aPKC mediates
Wnt signaling to regulate growth cone guidance, axon differentiation
and cell survival. Ryk is a Wnt repulsive receptor that regulates
axon guidance and inhibits regeneration after spinal cord injury.
aPKC expression was increased in motor neurons of the lumbar spinal
cord in SOD1 (G93A) mice at different stages. Interestingly, aPKC was
colocalized with SOD1 in motor neuron cell bodies and extracellular
aggregates, and aPKC-containing extracellular aggregates increased
with disease progression. Biochemical fractionation showed that aPKC
protein level was increased in the detergent-insoluble protein
fraction in SOD1 (G93A) mice at late stage but decreased in the
detergent-soluble fraction at symptomatic stage. These results
suggest that aPKC may be sequestered in SOD1 aggregates, impairing
its ability to protect motor neurons from death. Ryk expression was
also increased in the motor neurons and the white matter in the
ventral lumbar spinal cord of mutant SOD1 mice with a peak at early
stage. These observations indicate that Wnt/aPKC and Wnt/Ryk
signaling are altered in SOD1 (G93A) mice, suggesting that changed
Wnt signaling may contribute to neurodegeneration in ALS.
Please click here to download the PDF file.