| Summary: | <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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