Selective amputation of the pharynx identifies a FoxA-dependent regeneration program in planaria

Area of Science:

• Developmental Biology
• Regenerative Medicine
• Stem Cell Biology

Background:

• Planarian flatworms exhibit remarkable regenerative capabilities, regenerating any organ after amputation.
• Adult pluripotent stem cells are known to drive this regeneration.
• The precise mechanisms by which injury signals activate and direct these stem cells into specific lineages remain largely unknown.

Purpose of the Study:

• To develop a specific assay for studying single-organ regeneration in planarians.
• To identify genes essential for the regeneration of the planarian pharynx.
• To investigate the role of transcription factors, such as FoxA, in organ-specific regeneration.

Main Methods:

• A novel assay was established by selectively inducing pharynx ejection using sodium azide exposure.
• An RNA interference (RNAi) screen was conducted on 356 upregulated genes following amputation.
• Successful feeding was used as a phenotypic readout for successful pharynx regeneration.

Main Results:

• Knockdown of 20 screened genes resulted in diverse regeneration defects.
• RNAi targeting the forkhead transcription factor FoxA specifically blocked pharynx regrowth.
• FoxA is expressed in a subset of planarian stem cells, indicating its role in their differentiation.

Conclusions:

• Selective pharynx amputation provides a powerful model for identifying genes involved in organ-specific regeneration.
• The forkhead transcription factor FoxA plays a critical role in planarian pharynx regeneration.
• These findings suggest an evolutionarily conserved role for FoxA-dependent gene regulatory networks in driving regenerative processes.