Two novel type II receptors mediate BMP signalling and are required to establish left-right asymmetry in zebrafish

Research output: Contribution to journalArticle

Authors

  • Maarten van Dinther
  • Jeroen Bakkers
  • Robert Wilkinson
  • Roger Patient
  • Peter ten Dijke
  • Christine Mummery

Colleges, School and Institutes

External organisations

  • Hubrecht Laboratory KNAW (Netherlands Institute for Developmental Biology)
  • Leiden University Medical Center - LUMC
  • Interuniversity Cardiology Institute of the Netherlands ICIN - KNAW
  • Weatherall Institute of Molecular Medicine

Abstract

Ligands of the transforming growth factor β (TGFβ) superfamily, like Nodal and bone morphogenetic protein (BMP), are pivotal to establish left-right (LR) asymmetry in vertebrates. However, the receptors mediating this process are unknown. Here we identified two new type II receptors for BMPs in zebrafish termed bmpr2a and bmpr2b that induce a classical Smad1/5/8 response to BMP binding. Morpholino-mediated knockdown of bmpr2a and bmpr2b showed that they are required for the establishment of concomitant cardiac and visceral LR asymmetry. Expression of early laterality markers in morphants indicated that bmpr2a and bmpr2b act upstream of pitx2 and the nodal-related southpaw (spaw), which are expressed asymmetrically in the lateral plate mesoderm (LPM), and subsequently regulate lefty2 and bmp4 in the left heart field. We demonstrated that bmpr2a is required for lefty1 expression in the midline at early segmentation while bmpr2a/bmpr2b heteromers mediate left-sided spaw expression in the LPM. We propose a mechanism whereby this differential interpretation of BMP signalling through bmpr2a and bmpr2b is essential for the establishment of LR asymmetry in the zebrafish embryo.

Bibliographic note

Open Access under an Elsevier user licence - https://www.elsevier.com/about/our-business/policies/open-access-licenses/elsevier-user-license

Details

Original languageEnglish
Pages (from-to)55-71
Number of pages17
JournalDevelopmental Biology
Volume315
Issue number1
Publication statusPublished - 1 Mar 2008

Keywords

  • bmpr2a, bmpr2b, Cardiac laterality, Left-right asymmetry, Visceral laterality, Zebrafish