Role of Protocadherins in Zebrafish Neural Development

Bibliographic Details
Main Author:	Biswas, Sayantanee
Language:	English
Published:	The Ohio State University / OhioLINK 2012
Subjects:	Neurosciences Protocadherin zebrafish neural development
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=osu1354720718

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spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-osu13547207182021-08-03T06:06:47Z Role of Protocadherins in Zebrafish Neural Development Biswas, Sayantanee Neurosciences Protocadherin zebrafish neural development Dynamically regulated cell-cell adhesion is an important component of morphogenesis. Protocadherins comprise a newly discovered and highly conserved group of surface glycoproteins within the cadherin superfamily. Although, the protocadherins belong to the same superfamily as the classical cadherins, which are bona fide cell adhesion proteins, the role of protocadherins in cell-cell adhesion is not well understood. Due to the distinct expression patterns of protocadherins members in the nervous system, their isoform diversity, and frequent presence at synaptic junctions, it has been postulated that differential adhesive interactions among protocadherin members may provide a mechanism for selective cell-cell interaction during brain circuit formation. Although very little is known about the cellular roles of protocadherins, an increasing number of clinical studies show that protocadherins are involved in a wide range of neurodevelopmental disorders: Protocadherin-19 in Epilepsy and Mental Retardation limited to Females (EFMR), Protocadherin-17 in schizophrenia, and Protocadherin-18 in intellectual impairment. In this thesis using the zebrafish model organism, we have investigated the mRNA expression patterns of non-clustered protocadherin family members: Protocadherin-17 (Pcdh17), Protocadherin-19 (Pcdh19) and Protocadherin-18b (Pcdh18b). Each of the above mentioned non-clustered protocadherins exhibit dynamic expression in nervous system. In addition, we have characterized the detailed neuronal expression pattern of clustered protocadherins using antibodies generated against zebrafish Pcdh-α and Pcdh-γ. To understand the biological function of Pcdh19 and Pcdh18b, we performed loss-of-function studies using morpholino-mediated knockdown. In vivo two-photon imaging of embryos injected with Pcdh19-specific morpholinos revealed convergent cell movement defects in the anterior neural plate, which ultimately led to malformed brains. Further investigation indicated that Pcdh19 functions synergistically with Neural-cadherin (N-cadherin), a member of the classical cadherin family, during these convergent cell movements. Functional studies show a role of Pcdh18b in filopodial dynamics and arborization of caudal primary motor axons. In an attempt to characterize the adhesive property Pcdh19, we have discovered a novel mechanism of adhesion mediated by purified complexes of Protocadherins and Classical cadherin ectodomains, which is non-compatible with the strand-swap mechanism of adhesion seen in classical cadherins. Although, Pcdh19 and Pcdh17 did not show intrinsic adhesive activity, they formed cis-complexes with the classical cadherin member, N-cadherin, to mediate trans-homophilic interactions. Interestingly, in the complex-mediated bead aggregation, the protocadherins partner determined the adhesive interface and adhesive specificity of the complex. We thus propose a mechanism by which different combinations of Pcdh-Ncad molecules could provide cellular recognition and specify neuronal connections by mediating differential adhesiveness between neurons expressing different repertoires of protocadherins and classical cadherins. 2012-12-20 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1354720718 http://rave.ohiolink.edu/etdc/view?acc_num=osu1354720718 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	Neurosciences Protocadherin zebrafish neural development
spellingShingle	Neurosciences Protocadherin zebrafish neural development Biswas, Sayantanee Role of Protocadherins in Zebrafish Neural Development
author	Biswas, Sayantanee
author_facet	Biswas, Sayantanee
author_sort	Biswas, Sayantanee
title	Role of Protocadherins in Zebrafish Neural Development
title_short	Role of Protocadherins in Zebrafish Neural Development
title_full	Role of Protocadherins in Zebrafish Neural Development
title_fullStr	Role of Protocadherins in Zebrafish Neural Development
title_full_unstemmed	Role of Protocadherins in Zebrafish Neural Development
title_sort	role of protocadherins in zebrafish neural development
publisher	The Ohio State University / OhioLINK
publishDate	2012
url	http://rave.ohiolink.edu/etdc/view?acc_num=osu1354720718
work_keys_str_mv	AT biswassayantanee roleofprotocadherinsinzebrafishneuraldevelopment
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Role of Protocadherins in Zebrafish Neural Development

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