Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

You searched for id:"oai:etd.ohiolink.edu:kent1493679170223595". One record found.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


Kent State University

1. Jain, Shruti. Local translation of Down syndrome cell adhesion molecule and its implications for neural wiring defects.

Degree: PhD, College of Arts and Sciences / Department of Biological Sciences, 2017, Kent State University

Down syndrome cell adhesion molecule (Dscam) is known to play an important role in many neurodevelopmental processes such as axon guidance, dendrite arborization and synapse formation. DSCAM is located in the Down syndrome trisomic region of human chromosome 21 and implicated as one of the genes directly contributing to the Down syndrome brain phenotype, which includes a reduction in the formation of neuronal connectivity. The local translation of a select group of mRNA transcripts within growth cones is an important mechanism regulating axon guidance and is necessary for the formation of appropriate neuronal connectivity. Here, we find that netrin-1 stimulation induces DCC dependent local translation of Dscam mRNA in developing C57BL/6J mouse hippocampal growth cones. Furthermore, two RNA binding proteins, CPEB and FMRP, likely regulate Dscam mRNA localization and translation in hippocampal growth cones. Overexpression of DSCAM in mouse cortical pyramidal neurons results in a decrease in axon outgrowth and branching. This finding directly implicates DSCAM as a contributor to the formation of improper neuronal connectivity in Down syndrome. Interestingly, we have found that Dscam mRNA localization and translation is dysregulated in early postnatal Ts65Dn mice, a mouse model of Down syndrome. Ts65Dn growth cones also exhibit loss of responsiveness towards netrin-1, suggesting that the local translation of Dscam mRNA may be dysregulated in Down syndrome and contribute to disrupted axon guidance in this disorder. Ts65Dn hippocampal neurons display reduced axon length in vitro, as compared to their euploid littermates. In line with this, we find reduced interhemispheric connectivity in developing Ts65Dn mouse brains. Specifically, hippocampal commissure volume is reduced during brain development in Down syndrome, which likely contributes to the impaired learning and memory phenotype of this disorder. This study is the first to report the presence of defective interhemispheric connectivity at the time of birth in Ts65Dn mice, thus providing evidence that early therapeutic intervention may be the most effective time window for the treatment of Down syndrome. Thus, this study elucidates an important molecular mechanism underlying axon guidance that is dysregulated in Down syndrome mice, and likely contributes to inappropriate neural connectivity and the etiology of this neurodevelopmental disorder. Advisors/Committee Members: Welshhans, Kristy (Advisor).

Subjects/Keywords: Biology; Biomedical Research; Neurosciences; Local Translation; Axon growth and guidance; Down syndrome; Down syndrome cell adhesion molecule

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Jain, S. (2017). Local translation of Down syndrome cell adhesion molecule and its implications for neural wiring defects. (Doctoral Dissertation). Kent State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=kent1493679170223595

Chicago Manual of Style (16th Edition):

Jain, Shruti. “Local translation of Down syndrome cell adhesion molecule and its implications for neural wiring defects.” 2017. Doctoral Dissertation, Kent State University. Accessed August 23, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=kent1493679170223595.

MLA Handbook (7th Edition):

Jain, Shruti. “Local translation of Down syndrome cell adhesion molecule and its implications for neural wiring defects.” 2017. Web. 23 Aug 2017.

Vancouver:

Jain S. Local translation of Down syndrome cell adhesion molecule and its implications for neural wiring defects. [Internet] [Doctoral dissertation]. Kent State University; 2017. [cited 2017 Aug 23]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=kent1493679170223595.

Council of Science Editors:

Jain S. Local translation of Down syndrome cell adhesion molecule and its implications for neural wiring defects. [Doctoral Dissertation]. Kent State University; 2017. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=kent1493679170223595

.