The expression of twisted gastrulation in postnatal mouse brain and functional implications

M. Sun, C. Forsman, C. Sergi, R. Gopalakrishnan, M. B. O'Connor, A. Petryk

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Twisted gastrulation (TWSG1), an extracellular regulator of bone morphogenetic protein (BMP) signaling, is critical for embryonic brain development. Mice deficient in TWSG1 have abnormal forebrain development manifesting as holoprosencephaly. The expression and potential roles of TWSG1 in postnatal brain development are less well understood. We show that Twsg1 is expressed in the adult mouse brain in the choroid plexus (CP), hippocampus, and other regions, with the strongest expression observed in CP. TWSG1 was also detected in a human fetal brain at mid-gestation, with highest levels in the epithelium of CP. Bmp1, Bmp2, Bmp4-Bmp7 as well as BmprIA and BmprII, but not BmprIB, were expressed in CP. BMP antagonists Chordin (Chrd) and Noggin were not detected in CP, however Chrd-like 1 and brain-specific Chrd-like (Brorin) were expressed. Electrophysiological study of synaptic plasticity revealed normal paired-pulse facilitation and long-term potentiation in the CA1 region of hippocampus in Twsg1 -/- mice. Among the homozygous mutants that survive beyond the first 2 weeks, the prevalence of hydrocephalus was 4.3%, compared to 1.5% in a wild type colony (P=0.0133) between 3 and 10 weeks of life. We detected a high level of BMP signaling in CP in wild type adult mice that was 17-fold higher than in the hippocampus (P=0.005). In contrast, transforming growth factor beta (TGFβ) signaling was predominant in the hippocampus. Both BMP signaling and the expression of BMP downstream targets Msx1 and Msx2 were reduced in CP in Twsg1 -/- mice. In summary, we show that Twsg1 is expressed in the adult mouse and human fetal CP. We also show that BMP is a branch of TGFβ superfamily that is dominant in CP. This presents an interesting avenue for future research in light of the novel roles of CP in neural progenitor differentiation and neuronal repair, especially since TWSG1 appears to be the main regulator of BMP present in CP.

Original languageEnglish (US)
Pages (from-to)920-931
Number of pages12
Issue number2
StatePublished - Aug 2010

Bibliographical note

Funding Information:
M.B.O. is an Investigator with the Howard Hughes Medical Institute. This work was partially supported by the NIH grant R01DE016601 to A.P. The authors would like to thank Dr. Lothar Resch (University of Alberta Hospital) and Charles Billington (University of Minnesota) for helpful discussions, assistance with primer design and statistical analysis, and Robin Stocks (Department of Laboratory Medicine and Pathology, University of Alberta) for assistance with immunostaining.


  • BMP
  • Cerebrospinal fluid
  • Chordin-like
  • Choroid plexus
  • Hydrocephalus
  • Twsg1


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