Regeneration of the larval sea star nervous system by wounding induced respecification to the Sox2 lineage.

The ability to restore lost body parts following traumatic injury is a fascinating area of biology that challenges current understanding of the ontogeny of differentiation. The origin of new cells needed to regenerate lost tissue, and whether they are pluripotent or have de- or trans-differentiated, remains one of the most important open questions . Additionally, it is not known whether developmental gene regulatory networks are reused or whether regeneration specific networks are deployed. Echinoderms, including sea stars, have extensive ability for regeneration, however, the technologies for obtaining transgenic echinoderms are limited and tracking cells involved in regeneration, and thus identifying the cellular sources and potencies has proven challenging. In this study, we develop new transgenic tools to follow the fate of populations of cells in the regenerating larva of the sea star Patiria miniata . We show that the larval serotonergic nervous system can regenerate following decapitation. Using a BAC-transgenesis approach we show that expression of the pan ectodermal marker, sox2 , is induced in previously sox2 minus cells , even when cell division is inhibited. sox2 + cells give rise to new sox4 + neural precursors that then proceed along an embryonic neurogenesis pathway to reform the anterior nervous systems. sox2+ cells contribute to only neural and ectoderm lineages, indicating that these progenitors maintain their normal, embryonic lineage restriction. This indicates that sea star larval regeneration uses a combination of existing lineage restricted stem cells, as well as respecification of cells into neural lineages, and at least partial reuse of developmental GRNs to regenerate their nervous system.