Abstract

Mammalian spinal cord injury is an intractable biomedical problem driven by interlocking maladaptive cellular responses that prioritize acute stabilization over long-term recovery. However, this deficient regenerative capacity is not an inherent limitation. The zebrafish, for example, capably regenerates and regains motor function with 2 months of a full transection injury. This ability is thought to rely on the transient expansion of stem cell-like progenitors marked by sox2 expression. Yet our understanding of the identities and contributions of this crucial population remains limited. Here, we determine the molecular identities and cellular contributions of sox2+ progenitors during innate spinal cord repair in an adult zebrafish model. Genetic lineage tracing shows that, while they are quiescent in uninjured tissue, progenitors self-renew and differentiate into neurons and glia after injury. Single-cell sequencing reveals heterogeneous sox2+ populations biased toward neuronal or glial fates in both homeostatic and regenerating tissue. Further, we identify Bach1 as a dual activator and repressor of sox2 that is required for both transient activation of progenitors and their return to quiescence once repair is complete. Together, these studies transcriptionally map potent progenitors that support innate spinal cord repair and identify a molecular switch that regulates them through phase-dependent activation and repression.

Committee Chair

Mayssa Mokalled

Committee Members

Celeste Karch; Harrison Gabel; Lavinia Sheets; Phillip Williams

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

8-11-2026

Language

English (en)

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