SoxB1 Activity Regulates Sensory Neuron Regeneration, Maintenance, and Function in Planarians

Highlights

• soxB1-2-deficient planarians exhibit movement defects and abnormal sensory function

• Ectodermal-lineage progenitor cells express soxB1-2

• soxB1-2 activity is required for differentiation and function of sensory neurons

• Inhibition of genes downstream of soxB1-2 recapitulates sensory regeneration defects

Summary

SoxB1 genes play fundamental roles in neurodevelopmental processes and maintaining stem cell multipotency, but little is known about their function in regeneration. We addressed this question by analyzing the activity of the SoxB1 homolog soxB1-2 in the planarian Schmidtea mediterranea. Expression and functional analysis revealed that soxB1-2 marks ectodermal-lineage progenitors, and its activity is required for differentiation of subsets of ciliated epidermal and neuronal cells. Moreover, we show that inhibiting soxB1-2 or its candidate target genes leads to abnormal sensory neuron regeneration that causes planarians to display seizure-like movements or phenotypes associated with the loss of sensory modalities. Our analyses highlight soxB1-2-regulated genes that are expressed in sensory neurons and are homologous to factors implicated in epileptic disorders in humans and animal models of epilepsy, indicating that planarians can serve as a complementary model to investigate genetic causes of epilepsy.