Unravelling the genetic and molecular mechanisms of the left-right patterning genes Pkd1l1 and Pkd2

<p><i>Pkd1</i> and <i>Pkd2</i> encode the polycystin proteins which underlie human ADPKD, a major cause of end stage renal failure. Recently, by analysing the <i>Pkd2lrm4</i> mouse, a previous member of the lab provided evidence that loss of ciliary PKD2 und...

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Main Author: Dyer, LM
Other Authors: Norris, D
Format: Thesis
Language:English
Published: 2022
Subjects:
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author Dyer, LM
author2 Norris, D
author_facet Norris, D
Dyer, LM
author_sort Dyer, LM
collection OXFORD
description <p><i>Pkd1</i> and <i>Pkd2</i> encode the polycystin proteins which underlie human ADPKD, a major cause of end stage renal failure. Recently, by analysing the <i>Pkd2lrm4</i> mouse, a previous member of the lab provided evidence that loss of ciliary PKD2 underlies kidney cyst formation. Furthermore, the <i>Pkd2lrm4</i> mouse highlights a requirement for PKD2 in nodal cilia for correct L-R patterning. However, we are yet to fully understand its cilia-specific role and the mechanisms controlling its ciliary trafficking and entry. PKD1L1 (a PKD1 Paralog) functions with PKD2 in the embryonic node to allow correct L-R patterning and its expression and localisation during this process remain to be fully characterized.</p> <p>By generating endogenously tagged alleles of PKD1L1 and PKD2, I have investigated their localisation and co-localisation, in the embryonic node during L-R determination. Using these tagged alleles, <i>Pkd1l1mTFP1</i> and <i>Pkd2mNG</i>, I have been able to evaluate their localisation in <i>Pkd2</i>-/- and <i>Pkd1l1</i>-/- embryos respectively. Enabling us to further understand the role of their co-localisation, and assess the co-dependent relationship between PKD2 and PKD1L1 for ciliary localisation. Using <i>Pkd2lrm4/lrm4</i> samples, I have been able to identify a selection of candidate interacting proteins that may be involved in trafficking to cilia and ciliary entry of PKD2.</p> <p>The work in this thesis provides a new insight into the genetic and molecular mechanisms involved with the polycystins, and their roles in left-right pattern determination.</p>
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spelling oxford-uuid:07ab84f5-9cd6-4073-bfe8-9dfd24d5b73d2023-10-25T09:18:59ZUnravelling the genetic and molecular mechanisms of the left-right patterning genes Pkd1l1 and Pkd2Thesishttp://purl.org/coar/resource_type/c_db06uuid:07ab84f5-9cd6-4073-bfe8-9dfd24d5b73dDevelopmental biologyMolecular biologyGeneticsEnglishHyrax Deposit2022Dyer, LMNorris, DWhitby, M<p><i>Pkd1</i> and <i>Pkd2</i> encode the polycystin proteins which underlie human ADPKD, a major cause of end stage renal failure. Recently, by analysing the <i>Pkd2lrm4</i> mouse, a previous member of the lab provided evidence that loss of ciliary PKD2 underlies kidney cyst formation. Furthermore, the <i>Pkd2lrm4</i> mouse highlights a requirement for PKD2 in nodal cilia for correct L-R patterning. However, we are yet to fully understand its cilia-specific role and the mechanisms controlling its ciliary trafficking and entry. PKD1L1 (a PKD1 Paralog) functions with PKD2 in the embryonic node to allow correct L-R patterning and its expression and localisation during this process remain to be fully characterized.</p> <p>By generating endogenously tagged alleles of PKD1L1 and PKD2, I have investigated their localisation and co-localisation, in the embryonic node during L-R determination. Using these tagged alleles, <i>Pkd1l1mTFP1</i> and <i>Pkd2mNG</i>, I have been able to evaluate their localisation in <i>Pkd2</i>-/- and <i>Pkd1l1</i>-/- embryos respectively. Enabling us to further understand the role of their co-localisation, and assess the co-dependent relationship between PKD2 and PKD1L1 for ciliary localisation. Using <i>Pkd2lrm4/lrm4</i> samples, I have been able to identify a selection of candidate interacting proteins that may be involved in trafficking to cilia and ciliary entry of PKD2.</p> <p>The work in this thesis provides a new insight into the genetic and molecular mechanisms involved with the polycystins, and their roles in left-right pattern determination.</p>
spellingShingle Developmental biology
Molecular biology
Genetics
Dyer, LM
Unravelling the genetic and molecular mechanisms of the left-right patterning genes Pkd1l1 and Pkd2
title Unravelling the genetic and molecular mechanisms of the left-right patterning genes Pkd1l1 and Pkd2
title_full Unravelling the genetic and molecular mechanisms of the left-right patterning genes Pkd1l1 and Pkd2
title_fullStr Unravelling the genetic and molecular mechanisms of the left-right patterning genes Pkd1l1 and Pkd2
title_full_unstemmed Unravelling the genetic and molecular mechanisms of the left-right patterning genes Pkd1l1 and Pkd2
title_short Unravelling the genetic and molecular mechanisms of the left-right patterning genes Pkd1l1 and Pkd2
title_sort unravelling the genetic and molecular mechanisms of the left right patterning genes pkd1l1 and pkd2
topic Developmental biology
Molecular biology
Genetics
work_keys_str_mv AT dyerlm unravellingthegeneticandmolecularmechanismsoftheleftrightpatterninggenespkd1l1andpkd2