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Development 2014 Oct 01;14119:3740-51. doi: 10.1242/dev.106658.
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The splicing factor PQBP1 regulates mesodermal and neural development through FGF signaling.

Alternative splicing of pre-mRNAs is an important means of regulating developmental processes, yet the molecular mechanisms governing alternative splicing in embryonic contexts are just beginning to emerge. Polyglutamine-binding protein 1 (PQBP1) is an RNA-splicing factor that, when mutated, in humans causes Renpenning syndrome, an X-linked intellectual disability disease characterized by severe cognitive impairment, but also by physical defects that suggest PQBP1 has broader functions in embryonic development. Here, we reveal essential roles for PQBP1 and a binding partner, WBP11, in early development of Xenopus embryos. Both genes are expressed in the nascent mesoderm and neurectoderm, and morpholino knockdown of either causes defects in differentiation and morphogenesis of the mesoderm and neural plate. At the molecular level, knockdown of PQBP1 in Xenopus animal cap explants inhibits target gene induction by FGF but not by BMP, Nodal or Wnt ligands, and knockdown of either PQBP1 or WBP11 in embryos inhibits expression of fgf4 and FGF4-responsive cdx4 genes. Furthermore, PQBP1 knockdown changes the alternative splicing of FGF receptor-2 (FGFR2) transcripts, altering the incorporation of cassette exons that generate receptor variants (FGFR2 IIIb or IIIc) with different ligand specificities. Our findings may inform studies into the mechanisms underlying Renpenning syndrome.

PubMed ID: 25209246
PMC ID: PMC4197583
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: bmp4 cdx4 chrd fgf4 fgf8 fgfr2 gsc mapk1 myc ncam1 nodal nodal1 nodal2 nog odc1 pqbp1 sia1 snai2 sox2 szl tbxt tubb2b vegt wbp11 wnt8a
GO keywords: neural plate development [+]
Antibodies: Mapk Ab5 Mapk1 Ab7 Tubb2b Ab5
Morpholinos: pqbp1 MO1 pqbp1 MO2 pqbp1 MO3 pqbp1 MO4 wbp11 MO1

Disease Ontology terms: Renpenning syndrome
Phenotypes: Xla Wt + bmp4 + animal cap explant (Fig.6.A) [+]

Article Images: [+] show captions
References [+] :
Alexandrova, Smurf1 regulates neural patterning and folding in Xenopus embryos by antagonizing the BMP/Smad1 pathway. 2006, Pubmed, Xenbase