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TGF-beta coordinates changes in Keratin gene expression during complex tissue regeneration.

Dipak D Meshram1, Yuchang Liu1, Molly Worth1

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Zebrafish tail regeneration requires Hedgehog and TGF-beta signaling. Hedgehog activates TGF-beta, which regulates keratin genes (krt) involved in epithelial cell migration during repair.

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Area of Science:

  • Developmental Biology
  • Regenerative Medicine
  • Molecular Biology

Background:

  • Zebrafish tail regeneration involves wound repair, initiation, and redevelopment.
  • Hedgehog and TGF-beta signaling pathways are crucial for triggering tail regeneration.

Purpose of the Study:

  • To elucidate the roles of Hedgehog and TGF-beta signaling in zebrafish tail regeneration.
  • To identify genes regulated by these pathways during regeneration.

Main Methods:

  • Investigated gene expression changes after tail excision.
  • Analyzed TGF-beta-dependent gene expression.
  • Mapped expression of specific keratin genes (krt97, krt5).
  • Utilized single-cell RNA sequencing data.

Main Results:

  • Hedgehog signaling acts upstream of TGF-beta by inducing tgfb1a.
  • Keratin genes (krt) were categorized into TGF-beta-upregulated (krt_up) and downregulated (krt_down) sets.
  • krt97 (krt_up) is expressed in migrating epithelia, while krt5 (krt_down) is in stationary epithelia.
  • These keratin expression patterns are conserved during zebrafish development.

Conclusions:

  • Propose that krt_up facilitates collective epithelial migration, and krt_down inhibits it.
  • These findings reveal a mechanism for TGF-beta in initiating regeneration.
  • Suggests cytoskeletal changes influence cell movement during development and repair.