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ABSTRACT Tissue identity determination is crucial for regeneration, and the planarian anteroposterior (AP) axis uses positional control genes expressed from body wall muscle to determine body regionalization. Canonical Wnt signaling establishes anterior versus posterior pole identities through notum and wnt1 signaling, and two Wnt/FGFRL signaling pathways control head and trunk domains, but their downstream signaling mechanisms are not fully understood. Here, we identify a planarian Src homolog that restricts head and trunk identities to anterior positions. src-1(RNAi) animals formed enlarged brains and ectopic eyes and also duplicated trunk tissue, similar to a combination of Wnt/FGFRL RNAi phenotypes. src-1 was required for establishing territories of positional control gene expression in Schmidtea mediterranea, indicating that it acts at an upstream step in patterning the AP axis. Double RNAi experiments and eye regeneration assays suggest src-1 can act in parallel to at least some Wnt and FGFRL factors. Co-inhibition of src-1 with other posterior-promoting factors led to dramatic patterning changes and a reprogramming of Wnt/FGFRLs into controlling new positional outputs. These results identify src-1 as a factor that promotes robustness of the AP positional system that instructs appropriate regeneration.
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This content will become publicly available on November 1, 2025
Recording morphogen signals reveals mechanisms underlying gastruloid symmetry breaking
Aggregates of stem cells can break symmetry and self-organize into embryo-like structures with complex morphologies and gene expression patterns. Mechanisms including reaction-diffusion Turing patterns and cell sorting have been proposed to explain symmetry breaking but distinguishing between these candidate mechanisms of self-organization requires identifying which early asymmetries evolve into subsequent tissue patterns and cell fates. Here we use synthetic ‘signal-recording’ gene circuits to trace the evolution of signalling patterns in gastruloids, three-dimensional stem cell aggregates that form an anterior–posterior axis and structures resembling the mammalian primitive streak and tailbud. We find that cell sorting rearranges patchy domains of Wnt activity into a single pole that defines the gastruloid anterior–posterior axis. We also trace the emergence of Wnt domains to earlier heterogeneity in Nodal activity even before Wnt activity is detectable. Our study defines a mechanism through which aggregates of stem cells can form a patterning axis even in the absence of external spatial cues.
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- Award ID(s):
- 2134935
- PAR ID:
- 10557699
- Publisher / Repository:
- Nature Cell Biology
- Date Published:
- Journal Name:
- Nature Cell Biology
- Edition / Version:
- 26
- Volume:
- 26
- Issue:
- 11
- ISSN:
- 1465-7392
- Page Range / eLocation ID:
- 1832 to 1844
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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