The splicing factor PQBP1 regulates mesodermal and neural development through FGF signaling

Area of Science:

• Developmental biology
• Molecular biology
• Genetics

Background:

• Alternative splicing regulates gene expression during development.
• Mutations in Polyglutamine-binding protein 1 (PQBP1) cause Renpenning syndrome, a neurodevelopmental disorder.
• PQBP1's broader roles in embryonic development beyond intellectual disability are not fully understood.

Purpose of the Study:

• To investigate the roles of PQBP1 and its binding partner WBP11 in early Xenopus embryonic development.
• To elucidate the molecular mechanisms by which PQBP1 influences embryonic development, particularly concerning FGF signaling and alternative splicing.

Main Methods:

• Morpholino-mediated knockdown of PQBP1 and WBP11 in Xenopus embryos and animal cap explants.
• Analysis of gene expression and protein levels using RT-qPCR and Western blotting.
• Assessment of developmental defects in mesoderm and neural plate differentiation and morphogenesis.
• Investigation of alternative splicing patterns of FGF receptor-2 (FGFR2) transcripts.

Main Results:

• PQBP1 and WBP11 are expressed in the developing mesoderm and neurectoderm.
• Knockdown of PQBP1 or WBP11 leads to defects in mesoderm and neural plate development.
• PQBP1 knockdown impairs FGF-induced gene expression but not other signaling pathways.
• PQBP1 knockdown alters FGFR2 alternative splicing, affecting receptor variant generation.

Conclusions:

• PQBP1 and WBP11 play essential roles in early embryonic development, impacting mesoderm and neural plate formation.
• PQBP1 is critical for FGF signaling pathway activation and regulates alternative splicing of FGFR2.
• These findings provide insights into the molecular basis of Renpenning syndrome and PQBP1's function in development.