Browsing by Author "Nachtrab, Gregory"

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    Ras controls melanocyte expansion during zebrafish fin stripe regeneration.
    (Dis Model Mech, 2010-07) Lee, Yoonsung; Nachtrab, Gregory; Klinsawat, Pai W; Hami, Danyal; Poss, Kenneth D
    Regenerative medicine for complex tissues like limbs will require the provision or activation of precursors for different cell types, in the correct number, and with the appropriate instructions. These strategies can be guided by what is learned from spectacular events of natural limb or fin regeneration in urodele amphibians and teleost fish. Following zebrafish fin amputation, melanocyte stripes faithfully regenerate in tandem with complex fin structures. Distinct populations of melanocyte precursors emerge and differentiate to pigment regenerating fins, yet the regulation of their proliferation and patterning is incompletely understood. Here, we found that transgenic increases in active Ras dose-dependently hyperpigmented regenerating zebrafish fins. Lineage tracing and marker analysis indicated that increases in active Ras stimulated the in situ amplification of undifferentiated melanocyte precursors expressing mitfa and kita. Active Ras also hyperpigmented early fin regenerates of kita mutants, which are normally devoid of primary regeneration melanocytes, suppressing defects in precursor function and survival. By contrast, this protocol had no noticeable impact on pigmentation by secondary regulatory melanocyte precursors in late-stage kita regenerates. Our results provide evidence that Ras activity levels control the repopulation and expansion of adult melanocyte precursors after tissue loss, enabling the recovery of patterned melanocyte stripes during zebrafish appendage regeneration.
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    Understanding Positional Information During Zebrafish Fin Regeneration
    (2013) Nachtrab, Gregory

    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.