Understanding Positional Information During Zebrafish Fin Regeneration

Abstract

Regeneration is a remarkable feat that can only be accomplished by a small number of animals. The regeneration of vertebrate limbs is one such case as certain salamanders and fish regenerate robustly while mammalian ability to regenerate is extremely limited. Successful regeneration requires not just cell proliferation after injury but also the patterning of the new tissue into a suitable replacement structure. The process by which this patterning happens is referred to as positional memory. Identification of factors responsible for positional memory in vertebrate appendage regeneration has remained elusive. This dissertation establishes zebrafish pectoral fins as a model system for studying and defining positional memory factors. This has been accomplished through careful morphological measurements, gene expression profiling, construction of transgenic zebrafish strains, and the use of various chemical reagents. Two stunning examples of positional information in the pectoral fin have been discovered. First is the region-specific defect in male pectoral fin regeneration governed by an androgen's influence on GSK3 activity. The second is the role for hand2 in maintaining restricted vitamin D signaling and thus small bones in the posterior region of the pectoral fin. hand2 is the first defined positional memory factor in a zebrafish fin. However, in spite of this success the tools required for further dissection of positional memory are not available and thus the potential for meaningful future work is slight.