Proximo-distal positional information encoded by an Fgf-regulated gradient of homeodomain transcription factors in the vertebrate limb

Irene Delgado, Alejandra C. López-Delgado, Alberto Roselló Díez, Giovanna Giovinazzo, Vanessa Cadenas, Laura Fernández-De-Manuel, Fátima Sánchez-Cabo, Matthew J. Anderson, Mark Lewandoski, Miguel Torres

Research output: Contribution to journalArticleResearchpeer-review

31 Citations (Scopus)

Abstract

The positional information theory proposes that a coordinate system provides information to embryonic cells about their position and orientation along a patterning axis. Cells interpret this information to produce the appropriate pattern. During development, morphogens and interpreter transcription factors provide this information. We report a gradient of Meis homeodomain transcription factors along the mouse limb bud proximo-distal (PD) axis antiparallel to and shaped by the inhibitory action of distal fibroblast growth factor (FGF). Elimination of Meis results in premature limb distalization and HoxA expression, proximalization of PD segmental borders, and phocomelia. Our results show that Meis transcription factors interpret FGF signaling to convey positional information along the limb bud PD axis. These findings establish a new model for the generation of PD identities in the vertebrate limb and provide a molecular basis for the interpretation of FGF signal gradients during axial patterning.

Original languageEnglish
Article numbereaaz0742
Number of pages9
JournalScience Advances
Volume6
Issue number23
DOIs
Publication statusPublished - Jun 2020
Externally publishedYes

Keywords

  • Meis
  • limb development
  • Proximo-distal

Cite this