Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.624531
Keywords
left-right; cilia length; Pkd2; zebrafish; dand5; flow dynamics
Categories
Funding
- Fundacao para a Ciencia e a Tecnologia [FCT-ANR/BEX-BID/0153/2012, LISBOA-01-0145-FEDER-022170]
- FCT CEEC contract
- Sociedade Portuguesa de Nefrologia
- Fundacao para a Ciencia e Tecnologia/Ministerio da Educacao e Ciencia [iNOVA4Health UID/Multi/04462/2013]
- FEDER under the PT2020 Partnership Agreement [iNOVA4Health UID/Multi/04462/2013]
- Fundacao para a Ciencia e Tecnologia [PTDC/BEXBID/1411/2014]
- Fundacao para a Ciencia e Tecnologia
- research consortia Congento
- Lisboa Regional Operational Program (Lisboa2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)
- European Union [811087]
- Fundação para a Ciência e a Tecnologia [FCT-ANR/BEX-BID/0153/2012] Funding Source: FCT
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The reduction of Pkd2 leads to LR defects that cannot be solely attributed to its putative role in mediating mechanosensation, as it also affects LR flow dynamics through indirect mechanisms such as modifying cell shape and decreasing cilia length. Therefore, Pkd2 plays a crucial role in LR symmetry breaking mechanisms.
The left-right (LR) field recognizes the importance of the mechanism involving the calcium permeable channel Polycystin-2. However, whether the early LR symmetry breaking mechanism is exclusively via Polycystin-2 has not been tested. For that purpose, we need to be able to isolate the effects of decreasing the levels of Pkd2 protein from any eventual effects on flow dynamics. Here we demonstrate that curly-up (cup) homozygous mutants have abnormal flow dynamics. In addition, we performed one cell stage Pkd2 knockdowns and LR organizer specific Pkd2 knockdowns and observed that both techniques resulted in shorter cilia length and abnormal flow dynamics. We conclude that Pkd2 reduction leads to LR defects that cannot be assigned exclusively to its putative role in mediating mechanosensation because indirectly, by modifying cell shape or decreasing cilia length, Pkd2 deficit affects LR flow dynamics.
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