Development of a novel screening platform for identifying genetic pathways regulating axon regeneration

In the event of nervous system trauma, there are currently no treatments for functional loss due to thefailure of the mature mammalian central nervous system (CNS) to regenerate. Reduced intrinsic growth ability is believed to be a factor in attributing to the persistent functional deficits in neurological disorders such as spinal cord injury. Our candidate-based genetic screen allows us to examine and reveal several novel targets and pathways that have never been implicated in axon regeneration. However, we still lack a complete understanding of the repertoire of genetic factors that can promote or inhibit axonal regrowth after neural damage. Given that neurons have polarized morphology with distinct cellular compartments, microfluidic platforms had gained considerable impact in neuroscience research. Furthermore, disrupting gene expression is a common approach to understanding the loss-of-function disease mutations. Due to its many advantages, CRISPR technology is an attractive tool to irreversibly remove the gene of interest by targeting its DNA. The overall goal is to identify negative regulators in axon regeneration. Here, we performed candidatebased studies to assess novel candidates in neural regulation (Piezo, Atr, Nup188) and developed several novel axon transection microfluidics platforms that cater to various needs of current research. Results of this integrative approach can either be individually exploited to further neuroscience research or be taken together to result in a list of negative regulators that are potentially suitable as axon disconnection therapy targets.

Grantor dc:publisher

Temple University. Libraries

Year dc:date.issued

2022

Author dc:creator

• Lo, Tsz

Advisor dc:contributor.advisor

• Lelkes, Peter I.

Committee members dc:contributor.committeemember

• Song, Yunquan
• Lemay, Michel A.
• Spence, Andrew J.
• Matamoros, Andrew

• Bioengineering

Statement dc:rights

• IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/20.500.12613/8018

OAI identifier oai:identifier

oai:scholarshare.temple.edu:20.500.12613/8018