Stem cell-dependent formation of a functional anterior regeneration pole in planarians requires Zic and Forkhead transcription factors.
Planarians can regenerate their head within days. This process depends on the direction of adult stem cells to wound sites and the orchestration of their progenitors to commit to appropriate lineages and to arrange into patterned tissues. We identified a zinc finger transcription factor, Smed-ZicA, as a downstream target of Smed-FoxD, a Forkhead transcription factor required for head regeneration. Smed-zicA and Smed-FoxD are co-expressed with the Wnt inhibitor notum and the Activin inhibitor follistatin in a cluster of cells at the anterior-most tip of the regenerating head - the anterior regeneration pole - and in surrounding stem cell progeny. Depletion of Smed-zicA and Smed-FoxD by RNAi abolishes notum and follistatin expression at the pole and inhibits head formation downstream of initial polarity decisions. We suggest a model in which ZicA and FoxD transcription factors synergize to control the formation of Notum- and Follistatin-producing anterior pole cells. Pole formation might constitute an early step in regeneration, resulting in a signaling center that orchestrates cellular events in the growing tissue.
Max Planck Research Group Stem Cells & Regeneration, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Str. 54, 48149 Münster, Germany; Medical Faculty, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.
Matthias C
MC
Vogg
Max Planck Research Group Stem Cells & Regeneration, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Str. 54, 48149 Münster, Germany; Medical Faculty, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany; CiM-IMPRS Graduate School, Schlossplatz 5, 48149 Münster, Germany.
Suthira
S
Owlarn
Max Planck Research Group Stem Cells & Regeneration, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Str. 54, 48149 Münster, Germany; Medical Faculty, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.
Yuvia A
YA
Pérez Rico
MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Jianlei
J
Xie
CiM-IMPRS Graduate School, Schlossplatz 5, 48149 Münster, Germany; Planarian Stem Cell Laboratory, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Str. 54, 48149 Münster, Germany.
Yoko
Y
Suzuki
Planarian Stem Cell Laboratory, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Str. 54, 48149 Münster, Germany.
Luca
L
Gentile
MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Wei
W
Wu
Max Planck Research Group Stem Cells & Regeneration, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Str. 54, 48149 Münster, Germany; Medical Faculty, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany. Electronic address: kerstin.bartscherer@mpi-muenster.mpg.de.
Kerstin
K
Bartscherer
D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000502:physiology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D006257:Head / Q000502:physiology*; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D018613:Microscopy, Confocal; D008954:Models, Biological; D008969:Molecular Sequence Data; D010932:Planarians / Q000502:physiology*; D034622:RNA Interference; D012038:Regeneration / Q000502:physiology*; D017422:Sequence Analysis, DNA; D013234:Stem Cells / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology
D014157:Transcription Factors; D051153:Wnt Proteins
Follistatin; FoxD; Notum; Planaria; Regeneration; Stem cell differentiation; Zic