SEARCHOTHERpreclinical research, ophthalmology

other·preclinical research, ophthalmology, biomedical research, pediatric ophthalmology, neurology·PMC10912572

Prdm15 acts upstream of Wnt4 signaling in anterior neural development of Xenopus laevis

Frontiers in Cell and Developmental Biology · 8 authors, 4 centres

AI SUMMARY

FIDELITY 100%

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

Full summary

668 CHARS

This preclinical study used Xenopus laevis embryos to investigate the role of the zinc finger transcription factor Prdm15 in anterior neural development and its relevance to Galloway-Mowat syndrome (GAMOS). Prdm15 MO-injected embryos displayed a spectrum of anomalies from smaller and deformed eyes to complete absence of anterior head structures, including disrupted retinal lamination across multiple cell types and smaller lens expression domains. Reduced expression of key anterior neural marker genes upon Prdm15 knockdown was rescued by wnt4 RNA introduction. The findings demonstrate that Prdm15 acts upstream of both canonical and non-canonical Wnt4 signaling.

STUDY TYPE

other

SPECIALTY

preclinical research

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10912572

Prdm15 acts upstream of Wnt4 signaling in anterior neural development of Xenopus laevis

Frontiers in Cell and Developmental Biology

READ THE FULL PAPER

ABSTRACT

Mutations in PRDM15 lead to a syndromic form of holoprosencephaly (HPE) known as the Galloway–Mowat syndrome (GAMOS). While a connection between PRDM15, a zinc finger transcription factor, and WNT/PCP signaling has been established, there is a critical need to delve deeper into their contributions to early development and GAMOS pathogenesis. We used the South African clawed frog Xenopus laevis as the vertebrate model organism and observed that prdm15 was enriched in the tissues and organs affected in GAMOS. Furthermore, we generated a morpholino oligonucleotide–mediated prdm15 knockdown model showing that the depletion of Prdm15 leads to abnormal eye, head, and brain development, effectively recapitulating the anterior neural features in GAMOS. An analysis of the underlying molecular basis revealed a reduced expression of key genes associated with eye, head, and brain development. Notably, this reduction could be rescued by the introduction of wnt4 RNA, particularly during the induction of the respective tissues. Mechanistically, our data demonstrate that Prdm15 acts upstream of both canonical and non-canonical Wnt4 signaling during anterior neural development. Our findings describe severe ocular and anterior neural abnormalities upon Prdm15 depletion and elucidate the role of Prdm15 in canonical and non-canonical Wnt4 signaling.

CITATION EXPORT

Ernestine Saumweber, Slim Mzoughi, Arin Khadra et al.. Prdm15 acts upstream of Wnt4 signaling in anterior neural development of Xenopus laevis. Frontiers in Cell and Developmental Biology. (2024). https://doi.org/10.3389/fcell.2024.1316048

AUTHORS

8 · 4 CENTRES

Ernestine Saumweber, Slim Mzoughi, Arin Khadra, Anja Werberger, Sven Schumann, Ernesto Guccione, Michael J. Schmeisser, Susanne J. Kühl

1 Institute of Biochemistry and Molecular Biology, Ulm University, Ulm, Germany
2 Center of OncoGenomics and Innovative Therapeutics (COGIT), Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New-York, NY, United States
3 Institute of Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
4 Focus Program Translational Neurosciences, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany