Handling Editor: James Briscoe
ABSTRACT
Pathogenic mutations in the endocytic receptor LRP2 in humans are associated with severe neural tube closure defects (NTDs) such as anencephaly and spina bifida. Here, we have combined analysis of neural tube closure in mouse and in the African Clawed Frog Xenopus laevis to elucidate the etiology of Lrp2-related NTDs. Lrp2 loss of function impaired neuroepithelial morphogenesis, culminating in NTDs that impeded anterior neural plate folding and neural tube closure in both model organisms. Loss of Lrp2 severely affected apical constriction as well as proper localization of the core planar cell polarity (PCP) protein Vangl2, demonstrating a highly conserved role of the receptor in these processes, which are essential for neural tube formation. In addition, we identified a novel functional interaction of Lrp2 with the intracellular adaptor proteins Shroom3 and Gipc1 in the developing forebrain. Our data suggest that, during neurulation, motifs within the intracellular domain of Lrp2 function as a hub that orchestrates endocytic membrane removal for efficient apical constriction, as well as PCP component trafficking in a temporospatial manner.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: I.K., C.L., J.B.W., A.H., K.F.; Formal analysis: I.K.; Investigation: I.K., C.L., E.S., J.H., V.T., L.R., J.G., K.F.; Writing - original draft: I.K., A.H., K.F.; Writing - review & editing: I.K., C.L., J.B.W., A.H., K.F.; Visualization: I.K., C.L., K.F.; Supervision: J.B.W., A.H., K.F.; Project administration: J.B.W., A.H., K.F.; Funding acquisition: J.B.W., A.H., K.F.
Funding
A.H. was supported by the Deutsche Forschungsgemeinschaft, Collaborative Research Center (CRC958). I.K. was supported by the Deutsche Forschungsgemeinschaft Research Training Group grant (GRK2318, TJ-Train). K.F. was supported through a Margerete-von-Wrangell-Habilitationsstipendium, funded by the European Social Fund and by the Ministry of Science, Research and the Arts in Baden-Württemberg. C.L. and J.B.W. were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD099191) and the National Institute of General Medical Sciences (R01GM104853). Deposited in PMC for release after 12 months.
Supplementary information
Supplementary information available online at https://dev.biologists.org/lookup/doi/10.1242/dev.195008.supplemental
- Received July 16, 2020.
- Accepted December 11, 2020.
Log in using your username and password
Log in through your institution
Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$30.00 .
Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.
Article navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Other journals from The Company of Biologists
An interview with Swathi Arur
Swathi Arur joined the team at Development as an Academic Editor in 2020. Her lab uses multidisciplinary approaches to understand female germline development and fertility. We met with her over Zoom to hear more about her life, her career and her love for C. elegans.
Jim Wells and Hanna Mikkola join our team of Editors
We are pleased to welcome James (Jim) Wells and Hanna Mikkola to our team of Editors. Jim joins us a new Academic Editor, taking over from Gordan Keller, and Hanna joins our team of Associate Editors. Find out more about their research interests and areas of expertise.
New funding scheme supports sustainable events
As part of our Sustainable Conferencing Initiative, we are pleased to announce funding for organisers that seek to reduce the environmental footprint of their event. The next deadline to apply for a Scientific Meeting grant is 26 March 2021.
Read & Publish participation continues to grow
“I’d heard of Read & Publish deals and knew that many universities, including mine, had signed up to them but I had not previously understood the benefits that these deals bring to authors who work at those universities.”
Professor Sally Lowell (University of Edinburgh) shares her experience of publishing Open Access as part of our growing Read & Publish initiative. We now have over 150 institutions in 15 countries and four library consortia taking part – find out more and view our full list of participating institutions.
Upcoming special issues
Imaging Development, Stem Cells and Regeneration
Submission deadline: 30 March 2021
Publication: mid-2021
The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022
Both special issues welcome Review articles as well as Research articles, and will be widely promoted online and at key global conferences.
Development presents...
Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Here, Michèle Romanos talks about her new preprint, which mixes experimentation in quail embryos and computational modelling to understand how heterogeneity in a tissue influences cell rate.
Save your spot at our next session:
10 March
Time: 9:00 (GMT)
Chaired by: Thomas Lecuit
Join our mailing list to receive news and updates on the series.