BMP signalling controls the construction of vertebrate mucociliary epithelia

Development. 2015 Jul 1;142(13):2352-63. doi: 10.1242/dev.118679. Epub 2015 Jun 19.

Abstract

Despite the importance of mucociliary epithelia in animal physiology, the mechanisms controlling their establishment are poorly understood. Using the developing Xenopus epidermis and regenerating human upper airways, we reveal the importance of BMP signalling for the construction of vertebrate mucociliary epithelia. In Xenopus, attenuation of BMP activity is necessary for the specification of multiciliated cells (MCCs), ionocytes and small secretory cells (SSCs). Conversely, BMP activity is required for the proper differentiation of goblet cells. Our data suggest that the BMP and Notch pathways interact to control fate choices in the developing epidermis. Unexpectedly, BMP activity is also necessary for the insertion of MCCs, ionocytes and SSCs into the surface epithelium. In human, BMP inhibition also strongly stimulates the formation of MCCs in normal and pathological (cystic fibrosis) airway samples, whereas BMP overactivation has the opposite effect. This work identifies the BMP pathway as a key regulator of vertebrate mucociliary epithelium differentiation and morphogenesis.

Keywords: Airway; BMP; Epidermis; Human; Mucociliary epithelium; Multiciliogenesis; Notch; Xenopus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Lineage
  • Cells, Cultured
  • Cilia / metabolism*
  • Epidermal Cells
  • Epidermis / embryology
  • Epithelial Cells / metabolism
  • Epithelium / embryology*
  • Epithelium / metabolism*
  • Female
  • Humans
  • Lung / cytology
  • Regeneration
  • Signal Transduction*
  • Vertebrates / embryology*
  • Vertebrates / metabolism*
  • Xenopus
  • Xenopus Proteins / metabolism

Substances

  • Bone Morphogenetic Proteins
  • Xenopus Proteins