טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentKravtsov Veronika
SubjectBranching and Aging of Mechanosensory Neurons in C. elegans
DepartmentDepartment of Biology
Supervisor Professor Benjamin Podbilewicz
Full Thesis textFull thesis text - English Version


Abstract

Animals undergo aging-associated changes that ultimately lead to decreased functionality. The process of aging is under genetic control. The first and most prominent genetic pathway that regulates life-span has been discovered in the nematode Caenorhabditis elegans and it is the DAF-2/Insulin/IGF-1 pathway. Recent research has revealed that the nervous system of C. elegans undergoes alterations during aging, which are postponed in the long lived daf-2 mutants. In humans many neurodegenerative diseases as well as generalized cognitive decline are associated with age, aberrant dendritic arborization or both (e.g. autism and Alzheimer's disease).

I study dendritic plasticity, neuronal auto-fusion and aging of two highly arborized multimodal mechanoreceptors required for sensing cold and harsh-touch noxious stimuli in C. elegans, the PVDs. The PVD neuron is used as a model for dendritic arborization and response to injury and trauma. Its dendritic tree is composed of a repetitive unit that is named "menorah". The fusion protein EFF-1 has been shown to sculpt these menorahs in a PVD cell autonomous manner. Moreover, PVD dendritic trees of young adults are highly plastic and show very robust regenerative ability following dendrotomy (laser induced severing of dendrites). A second eukaryotic fusion protein, AFF-1, is required for menorah-menorah fusion that enables regeneration of severed dendrites.

This work provides characterization of the alterations that the PVD dendrites undergo during aging in terms of morphology, function and response to injury. The main findings are: 1) During normal aging and in daf-2 mutant background menorahs appear disorganized, hyperbranched around cell-body and overlapped. 2) EFF-1 overexpression in the PVD brings to simplification of the menorahs during aging. 3) Response to harsh touch slightly declines during aging, again both in wild-type and daf-2 mutant backgrounds. 4) Dendrotomized dendrites of "aged” wild type individuals fail to regenerate, which ultimately leads to degeneration of the distal stump. 5) DAF-2 decrease of function postpones the regenerative decline. 6) AFF-1 overexpression in the PVD is sufficient to drive "aged" dendrites into successful regeneration.

Overall this research provides an insight into the aging of individual neurons and suggests an important role for fusion in maintenance of dendritic morphology and regeneration.