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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Format: | Thesis |
Language: | English |
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2022
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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> |
first_indexed | 2024-03-07T08:04:31Z |
format | Thesis |
id | oxford-uuid:07ab84f5-9cd6-4073-bfe8-9dfd24d5b73d |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T08:04:31Z |
publishDate | 2022 |
record_format | dspace |
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 |