Mutations in gfpt1 and skiv2l2 cause distinct stage-specific defects in larval melanocyte regeneration in zebrafish

Abstract

The establishment of a single cell type regeneration paradigm in the zebrafish provides an opportunity to investigate the genetic mechanisms specific to regeneration processes. We previously demonstrated that regeneration melanocytes arise from cell division of the otherwise quiescent melanocyte precursors following larval melanocyte ablation with a small molecule, MoTP. The ease of ablating melanocytes by MoTP allows us to conduct a forward genetic screen for mechanisms specific to regeneration from such precursors or stem cells. Here, we reported the identification of two mutants, eartha j23e1 and julie j24e1 from a melanocyte ablation screen. Both mutants develop normal larval melanocytes, but upon melanocyte ablation, each mutation results in a distinct stage-specific defect in melanocyte regeneration. Positional cloning reveals that the eartha j23e1 mutation is a nonsense mutation in gfpt1 (glutamine:fructose-6-phosphate aminotransferase 1), the rate-limiting enzyme in glucosamine-6-phosphate biosynthesis. Our analyses reveal that a mutation in gfpt1 specifically affects melanocyte differentiation (marked by melanin production) at a late stage during regeneration and that gfpt1 acts cell autonomously in melanocytes to promote ontogenetic melanocyte darkening. We identified that the julie j24e1 mutation is a splice-site mutation in skiv2l2 (superkiller viralicidic activity 2-like 2), a predicted DEAD-box RNA helicase. Our in situ analysis reveals that the mutation in skiv2l2 causes defects in cell proliferation, suggesting that skiv2l2 plays a role in regulating melanoblast proliferation during early stages of melanocyte regeneration. This finding is consistent with previously described role for cell division during larval melanocyte regeneration. The analyses of these mutants reveal their stage-specific roles in melanocyte regeneration. Interestingly, these mutants identify regeneration-specific functions not only in early stages of the regeneration process, but also in late stages of differentiation of the regenerating melanocyte. We suggest that mechanisms of regeneration identified in this mutant screen may reveal fundamental differences between the mechanisms that establish differentiated cells during embryogenesis, and those involved in larval or adult growth.Citation: Yang CT, Hindes AE, Hultman KA, Johnson SL (2007) Mutations in gfpt1 and skiv2l2 cause distinct stage-specific defects in larval melanocyte regeneration in zebrafish. PLoS Genet 3(6): e88.

Ethylnitrosourea‐induced thymus‐defective mutants identify roles ofKIAA1440, TRRAP, andSKIV2L2in teleost organ development

“…SKIV2L2 was expressed widely in adult medaka organs (data not shown) as well as in stage 36 (6 dpf) embryos, in agreement with the analysis of SKIV2L2 in zebrafish [27].…”

“…1). These results suggest that the defective splicing of SKIV2L2 mRNA caused by a point mutation at the splicing donor site is responsible for the hjc phenotypes.SKIV2L2 was expressed widely in adult medaka organs (data not shown) as well as in stage 36 (6 dpf) embryos, in agreement with the analysis of SKIV2L2 in zebrafish [27]. …”

“…SKIV2L2 encoded by the hjc allele likely lacks the histone deacetylase interacting domain completely. A recent article reported that the zebrafish SKIV2L2 mutant julie is defective in the regeneration of melanocytes and tail [27]; thus, it would be interesting to examine further whether julie mutants are defective in thymus development in zebrafish.…”

Monitoring Sentinel of Diarrhea: A Rotavirus in the Site of Hospital Complex Pediatrique of Kingasani II: 2009-2014

“…However, from there until October 2014, we recorded 1204 cases of acute gastroenteritis and these cases were included in the data recorded in the national surveillance system [20].…”

Effect of Early Introduction of Microencapsulated Diet to Larval Atlantic Halibut, Hippoglossus hippoglossus L. Assessed by Microarray Analysis

“…It is expressed throughout the central nervous system, especially in the spinal cord in humans and mice and has been implicated in type II diabetes (Zhang et al 2004). Interestingly, the isozyme Gfpt1 promotes ontogenetic melanocyte darkening (Yang et al 2007). In our study, Gfpt2 was moderately upregulated in fish fed the microdiet.…”