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Epithelial Migration and Non-adhesive Periderm Are Required for Digit Separation during Mammalian Development.

  • Author(s): Kashgari, Ghaidaa
  • Meinecke, Lina
  • Gordon, William
  • Ruiz, Bryan
  • Yang, Jady
  • Ma, Amy Lan
  • Xie, Yilu
  • Ho, Hsiang
  • Plikus, Maksim V
  • Nie, Qing
  • Jester, James V
  • Andersen, Bogi
  • et al.
Abstract

The fusion of digits or toes, syndactyly, can be part of complex syndromes, including van der Woude syndrome. A subset of van der Woude cases is caused by dominant-negative mutations in the epithelial transcription factor Grainyhead like-3 (GRHL3), and Grhl3-/-mice have soft-tissue syndactyly. Although impaired interdigital cell death of mesenchymal cells causes syndactyly in multiple genetic mutants, Grhl3-/- embryos had normal interdigital cell death, suggesting alternative mechanisms for syndactyly. We found that in digit separation, the overlying epidermis forms a migrating interdigital epithelial tongue (IET) when the epithelium invaginates to separate the digits. Normally, the non-adhesive surface periderm allows the IET to bifurcate as the digits separate. In contrast, in Grhl3-/- embryos, the IET moves normally between the digits but fails to bifurcate because of abnormal adhesion of the periderm. Our study identifies epidermal developmental processes required for digit separation.

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