Planar Cell Polarity function of the Wnt co-receptor Lrp5/6-Arrow
NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development
About This Grant
Child development and organogenesis depend on a highly regulated interplay of inductive events, which are regulated by evolutionarily conserved cell signaling pathways. Wnt-signaling pathways are a signaling system, conserved across the animal kingdom and regulating early development by inductive events and subsequent cell growth, cell fate, and cell polarity across whole organisms and during organogenesis in the whole body. Wnt-signaling is also critical in stem cell establishment and maintenance of (almost) all tissues. At the center of these pathways are the Wnt morphogens and their receptors, the Frizzled family (Fz in Drosophila, and Fzd in mammals) of 7-pass trans-membrane proteins. The canonical Wnt-pathway also critically employs the LRP5/6 co-receptors (known as Arrow in Drosophila). While a lot is known about the architecture of the two main Wnt-pathways: the canonical Wnt/-catenin pathway and Wnt/PCP (Planar Cell Polarity) signaling, and the membrane protein complex associated activation of the canonical pathway, employing Fzd-LRP5/6 heteromeric complexes for Wnt binding, much less is known about the activation of Wnt/PCP signaling, leading to asymmetric PCP complex localization and hence cell polarity. We have strong preliminary evidence for a critical role of Arrow-LRP5/6 in Wnt/PCP signaling, which we propose to address in this application. Regulation of Wnt-signaling specificity between the Wnt/-catenin pathway and Wnt/PCP signaling remains unclear, and has so far largely been linked to the presumed specific role of Arrow-LRP5/6 in the Wnt/-catenin pathway, and differential recruitment of Dishevelled (Dsh/Dvl) proteins as the cytoplasmic mediators of Wnt- receptor interactions. As Dsh is at the node of all Wnt-signaling events and the pathways are sensitive to levels of Dsh/Dvl, we have designed and utilized a genome-wide genetic screen in Drosophila to identify novel “pathway specificity”-regulators of Wnt-signaling activation. Strikingly, this screen has revealed a critical role of Arrow-LRP5/6 in both pathways, including Wnt-PCP signaling, while it is presumed to be Wnt/-catenin pathway specific as outlined above. We are proposing here to functionally define and dissect the role of Arrow- LRP5/6 in Wnt-PCP signaling. This new function of Arrow-LRP5/6 in Wnt/PCP signaling is very unexpected and intriguing, as it challenges the pathway architecture as presented in text books, and thus it is an exciting and challenging new research avenue in the Wnt-signaling context. The specific Aims are to (1) define the phenotypic requirements of Arrow-LRP5/6 in Wnt-PCP signaling, and (2) establish the molecular mechanisms of how Arrow-LRP5/6 intersects with the well-known PCP-Core factors, including the PCP dedicated Fz receptor subset(s) and the shared effector Dsh. Our preliminary data suggest that Arrow-LRP5/6 promotes Fz- PCP signaling, acting positively upstream of Dsh in the PCP complex formation. Information acquired in this application will advance our mechanistic understanding of Arrow-LRP5/6 in the Wnt-pathways, and potentially could also lead to follow up studies in developmental disease associated contexts.
Grant Summary
Planar Cell Polarity function of the Wnt co-receptor Lrp5/6-Arrow is a NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development grant providing up to $465K for university, nonprofit, healthcare org. Applications are due 2028-05-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $465K
2028-05-31
- 1Confirm your organization is eligible for Planar Cell Polarity function of the Wnt co-receptor Lrp5/6-Arrow from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development before the deadline.
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Planar Cell Polarity function of the Wnt co-receptor Lrp5/6-Arrow: Frequently Asked Questions
Who is eligible for the Planar Cell Polarity function of the Wnt co-receptor Lrp5/6-Arrow?
Planar Cell Polarity function of the Wnt co-receptor Lrp5/6-Arrow is offered by NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Planar Cell Polarity function of the Wnt co-receptor Lrp5/6-Arrow provide?
Planar Cell Polarity function of the Wnt co-receptor Lrp5/6-Arrow provides up to $465K per award from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Planar Cell Polarity function of the Wnt co-receptor Lrp5/6-Arrow deadline?
Applications for Planar Cell Polarity function of the Wnt co-receptor Lrp5/6-Arrow are due 2028-05-31 (open). Because deadlines can change, verify the date with the funder, NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Planar Cell Polarity function of the Wnt co-receptor Lrp5/6-Arrow?
To apply for Planar Cell Polarity function of the Wnt co-receptor Lrp5/6-Arrow, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development.