Enhanced BMP signaling through ALK2 attenuates keratinocyte differentiation

Biochem Biophys Res Commun. 2022 Nov 12:629:101-105. doi: 10.1016/j.bbrc.2022.09.014. Epub 2022 Sep 10.


Accumulated studies have suggested that bone morphogenetic proteins (BMPs) are critical for skin development. However, it remains elusive how BMP signaling via ALK2 (aka ACVR1), one of the important BMP type I receptors, regulates keratinocyte differentiation. To address this question, we utilized a genetic system that enhances BMP signaling via ALK2 in an epidermis-specific manner in mice (hereafter ca-Alk2:K14-Cre). Ca-Alk2:K14-Cre mice displayed a sticky and hairless skin phenotype with a thinner epidermis incapable of differentiating. Although cellular proliferation and survival were comparable between wild-type and ca-Alk2:K14-Cre mice, skin differentiation was severely hampered in ca-Alk2:K14-Cre mice. To uncover the mechanism of altered keratinocyte differentiation, we performed a transcriptome analysis. As a result, we found that the expression levels of cell cycle inhibitor p21 were increased in ca-Alk2:K14-Cre mice. Our findings suggest that aberrant BMP signaling via ALK2 positively regulates p21 expression that attenuates keratinocyte differentiation, and further highlights the critical role of BMP signaling in skin development.

Keywords: ALK2; BMP signaling; Mouse; Skin; p21.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Activin Receptors, Type I* / genetics
  • Activin Receptors, Type I* / metabolism
  • Animals
  • Bone Morphogenetic Protein Receptors, Type I / genetics
  • Bone Morphogenetic Protein Receptors, Type I / metabolism
  • Bone Morphogenetic Proteins* / metabolism
  • Cell Differentiation / genetics
  • Keratinocytes / metabolism
  • Mice
  • Signal Transduction / genetics


  • Bone Morphogenetic Proteins
  • Activin Receptors, Type I
  • Acvr1 protein, mouse
  • Bone Morphogenetic Protein Receptors, Type I