Abstract
Regeneration is initiated by wounding, but it is unclear how injury-induced signals precisely convey the identity of the tissues requiring replacement. In the planarian Schmidtea mediterranea, the first event in head regeneration is the asymmetric activation of the Wnt inhibitor notum in longitudinal body-wall muscle cells, preferentially at anterior-facing versus posterior-facing wound sites. However, the mechanism driving this early symmetry-breaking event is unknown. We identify a noncanonical Wnt11 and Dishevelled pathway regulating notum polarization, which opposes injury-induced notum-activating Wnt/β-catenin signals and regulates muscle orientation. Using expression analysis and experiments to define a critical time of action, we demonstrate that Wnt11 and Dishevelled signals act prior to injury and in a growth-dependent manner to orient the polarization of notum induced by wounding. In turn, injury-induced notum dictates polarization used in the next round of regeneration. These results identify a self-reinforcing feedback system driving the polarization of blastema outgrowth and indicate that regeneration uses pre-existing tissue information to determine the outcome of wound-induced signals.
Original language | English (US) |
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Pages (from-to) | 5262-5273.e2 |
Journal | Current Biology |
Volume | 32 |
Issue number | 24 |
DOIs | |
State | Published - Dec 19 2022 |
Funding
We thank members of the Petersen lab for critical comments. The authors acknowledge funding from the National Institutes of Health , USA ( NIGMS R01GM129339 and R01GM130835 ) (C.P.P.), and Northwestern’s NIH Cellular and Molecular Basis of Disease Training Program 2T32GM008061 (D.I.G.).
Keywords
- Dishevelled
- Wnt
- Wnt11
- blastema
- injury signaling
- muscle
- notum
- planaria
- polarity
- regeneration
ASJC Scopus subject areas
- General Agricultural and Biological Sciences
- General Biochemistry, Genetics and Molecular Biology
- General Neuroscience