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| Item Type: | Article |
|---|---|
| Title: | Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling |
| Creators Name: | Kocere, Agnese, Chiavacci, Elena, Soneson, Charlotte, Jacobson, Seth T, Harrison, Emma N, Méndez-Acevedo, Kevin Manuel, MacGowan, Jacalyn S, Wells, Harrison H, Hiltabidle, Max S, Raghunath, Azhwar, Shavit, Jordan A, Panáková, Daniela, Williams, Margot L K, Robinson, Mark D, Mosimann, Christian and Burger, Alexa |
| Abstract: | Thrombocytopenia-Absent Radius (TAR) syndrome is a rare congenital condition with reduced platelets, forelimb anomalies, and variable heart and kidney defects. TAR syndrome is caused by mutations in RBM8A/Y14, a component of the exon junction complex. How perturbing a general mRNA-processing factor causes the selective TAR Syndrome phenotypes remains unknown. Here, we connect zebrafish rbm8a perturbation to early hematopoietic defects via attenuated non-canonical Wnt/Planar Cell Polarity (PCP) signaling. In hypomorphic rbm8a zebrafish, we observe a reduction of cd41-positive thrombocytes. rbm8a-mutant zebrafish accumulate mRNAs with retained introns, including non-canonical Wnt/PCP pathway components resulting in convergent extension defects. We found that reduced rbm8a function interacts with perturbations in non-canonical Wnt/PCP pathway genes wnt5b, wnt11f2, fzd7a, and vangl2, impairing the architecture of the lateral plate mesoderm (LPM) that forms hematopoietic, cardiovascular, kidney, and forelimb skeleton progenitors. Both mutants for rbm8a and for the PCP gene vangl2 feature impaired expression of early hematopoietic/endothelial genes runx1 and gfi1aa. Together, our data propose aberrant LPM patterning and hematopoietic defects as consequence of attenuated non-canonical Wnt/PCP signaling upon reduced rbm8a function. |
| Keywords: | Hematopoiesis, Non-Canonical Wnt, Development, Thrombocytopenia, Morphogenesis, Animals, Zebrafish |
| Source: | Developmental Biology |
| ISSN: | 0012-1606 |
| Publisher: | Elsevier / Academic Press |
| Volume: | 528 |
| Page Range: | 34-56 |
| Date: | December 2025 |
| Official Publication: | https://doi.org/10.1016/j.ydbio.2025.08.021 |
| PubMed: | View item in PubMed |
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