Language

English

Publication Date

12-1-2025

Journal

Developmental Biology

DOI

10.1016/j.ydbio.2025.08.021

PMID

40907933

PMCID

PMC12863336

PubMedCentral® Posted Date

2-3-2026

PubMedCentral® Full Text Version

Author MSS

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

Animals, Zebrafish, Zebrafish Proteins, RNA-Binding Proteins, Wnt Signaling Pathway, Cell Polarity, Hematopoiesis, Thrombocytopenia, Gene Expression Regulation, Developmental, Mutation, Mesoderm, Radius, Zebrafish, Hematopoiesis, Non-canonical wnt, Development, Thrombocytopenia, Morphogenesis

Published Open-Access

yes

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