THESIS
2013
xvi, 91 p. : ill. (some col.) ; 30 cm
Abstract
Adult neurogenesis, generation of mammalian new neurons throughout
adulthood, occurs in two restricted regions in the brain- the subventricular zone
of lateral ventricle and the subgranular zone of dentate gyrus in hippocampus.
Hippocampal neurogenesis has been suggested to be a new mechanism that
mediates learning and memory. It is a complex process including proliferation of
neural progenitor cells, neuronal differentiation, maturation and functional
integration. To ensure proper neurogenesis, the organization and dynamics of
cytoskeletal network has to be precisely regulated and tightly coordinated.
A GTPase activating protein (GAP) α2-chimaerin regulates the organization
and dynamics of actin and microtubule cytoskeletal network. α2-chimaerin
regulates axon guidance in d...[
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Adult neurogenesis, generation of mammalian new neurons throughout
adulthood, occurs in two restricted regions in the brain- the subventricular zone
of lateral ventricle and the subgranular zone of dentate gyrus in hippocampus.
Hippocampal neurogenesis has been suggested to be a new mechanism that
mediates learning and memory. It is a complex process including proliferation of
neural progenitor cells, neuronal differentiation, maturation and functional
integration. To ensure proper neurogenesis, the organization and dynamics of
cytoskeletal network has to be precisely regulated and tightly coordinated.
A GTPase activating protein (GAP) α2-chimaerin regulates the organization
and dynamics of actin and microtubule cytoskeletal network. α2-chimaerin
regulates axon guidance in developing corticospinal tract through its GAP
activity towards Rac1, and modulates neuronal migration in cerebral cortex via
the SH2 domain. While α2-chimaerin is highly expressed in the adult mouse
hippocampus, its specific function in hippocampus remains unclear. We aim to
investigate whether α2-chimaerin is involved in adult neurogenesis in
hippocampus. We found that the number of both newly-born cells and actively
proliferating neuronal precursors was dramatically reduced in the subgranular
zone of dentate gyrus in adult α2-chimaerin null mice. Furthermore, the number
of immature neurons was also reduced. Together, we demonstrated that
α2-chimaerin is critical for both amplification of neuronal progenitor cells and
neuronal differentiation in adult neurogenesis.
In future, we will investigate the mechanisms underlying the
α2-chimaerin-mediated regulation of proliferation/differentiation of neuronal
precursors and whether the loss of α2-chimearin leads to aberrant brain function
in adult mice.
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