Stem cells and neural regeneration
Unlike most organisms, planarians can be decapitated and regenerate a new pair of eyes, a brain, and functionally reintegrate new tissue with old in approximately 7 days. In addition, they have unlimited capacity to perform this regenerative task and do so without scarring. We have several big questions we are investigating as to how this amazing biology works:
- Do planarians have neural stem cells?
- Do planarians use homologs of key transcription factors used in embryonic neural development in other model systems to accomplish neural regeneration?
- How do new neurons find their synaptic partners in old tissue to restore function?
A hypothesized lineage example is shown below.
Do planarians have neural stem cells?
To tackle this question, we have turned to single-cell RNA sequencing (scRNAseq). We have found that there exists a type of stem cell in planarians that has neural character by scRNAseq (below). We are now working on identifying the transcription factors that specify the neural-biased stem cell.
Do planarians use homologs of key transcription factors used in embryonic neural development in other model systems to accomplish neural regeneration?
We have performed RNAi screens on over 200 transcription factors to identify ones that direct the specification or patterning of neural subtypes. We have uncovered many interesting factors, but importantly, there appears to be two major pathways for a new neuron to integrate into the brain. Either a cell is going to be ventral medial or dorsal lateral. We have found that a tcf homolog, tcf-1, specifies new neurons to a dorsal lateral fate while arx and nkx2 homologs specify neurons to ventral medial fates.
We are now combining RNAi phenotypes with the scRNAseq data to computationally predict routes of differentiation, which we then test in vivo.
How do new neurons find their synaptic partners in the old tissue?
Little is known about this biology in planarians, so we are performing RNAi screens of candidate molecules. In addition, this question can be addressed in the zebrafish model of spinal cord regeneration. Stay tuned to what we find out!
