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Expression and function of semaphorin4F in the developing and adult rat nervous system

University of British Columbia

Traumatic injury to the mature peripheral or central nervous system results in different regenerative outcomes. In the peripheral nervous system (PNS), neurons that suffer an axonal injury will typically mount a successful regenerative response, leading to target reinnervation and functional recovery. Conversely, in the central nervous system (CNS), neurons do not mount a strong regenerative response after axonal injury, and thus fail to regenerate and functionally reinnervate their targets. This lack of CNS axonal regeneration and functional recovery is manifested in the permanent and devastating paralysis endured by individuals who suffer a spinal cord injury. Given the dissimilar regenerative outcomes between the CNS and PNS, elucidating the factors that contribute to this distinction--particularly those that promote successful regeneration in the PNS--may help us develop methods by which to promote functional regeneration of injured adult CNS neurons. Semaphorins are a family of growth-promoting (chemoattractive) and growth-inhibiting (chemorepulsive) proteins that, by virtue of their influence on axonal growth, may be important factors in regeneration after injury. In this thesis, I examined the expression of one member of this family, Semaphorin4F (Sema4F), in the adult vertebrate nervous system following axonal injury. I addressed the question: Does the expression of Sema4F in axotomized neurons coincide with the regenerative potential of the injured neuronal population? I found that neuronal populations able to mount a robust regenerative response after axonal injury also upregulate their expression of Sema4F, a process not observed in neurons lacking this response. This correlation between Sema4F expression following axotomy and the regenerative ability of the particular adult neuronal population suggests that Sema4F may play a positive role in the regenerative process. Furthermore, I also asked the question: Can Sema4F inhibit the extension of embryonic sensory neurites in culture? I determined that while neuronally-expressed Sema4F may function as a growth promoting cue in the injured adult PNS, in vitro , it functions as a membrane-bound, non-permissive cue to ’slow’ or ’stall’ the extension of embryonic-day-13 DRG neurites across HEK 293 cell islands. These findings suggest that Sema4F may play a multifaceted role in the developing and mature nervous system.

Text

2010-01-18

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http://hdl.handle.net/2429/18615

Zoology

University of British Columbia

Graduate