Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling
Agnese Kocere1,2, Elena Chiavacci2, Charlotte Soneson2,3
1Department of Pediatrics, Section of Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Biorxiv : the Preprint Server for Biology
|April 24, 2023
Summary
Defects in Thrombocytopenia-Absent Radius (TAR) syndrome stem from impaired mRNA processing by RBM8A, leading to reduced platelet production and forelimb anomalies. This study links TAR syndrome to disrupted Wnt/Planar Cell Polarity signaling and abnormal embryonic development.
Area of Science:
- Developmental Biology
- Genetics
- Hematology
Background:
- Thrombocytopenia-Absent Radius (TAR) syndrome is a rare congenital disorder characterized by low platelet counts and limb abnormalities.
- TAR syndrome is associated with reduced function of the RBM8A gene, a key component of the mRNA processing machinery.
- The precise mechanism by which RBM8A dysfunction leads to TAR syndrome phenotypes remains unclear.
Conclusions:
- Aberrant lateral plate mesoderm (LPM) patterning due to attenuated non-canonical Wnt/Planar Cell Polarity (PCP) signaling underlies the hematopoietic and developmental defects in TAR syndrome.
- These findings suggest a potential LPM origin for TAR syndrome and elucidate a novel developmental mechanism.
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