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Cited by 87Biochemical and Molecular Researchmelanin and skin pigmentationZebrafish Biomedical Research Applications

Zebrafish mutations in gart and paics identify crucial roles for de novo purine synthesis in vertebrate pigmentation and ocular development

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Ng, Anthony, Uribe, Rosa A., Yieh, Leah, Nuckels, Richard, Gross, Jeffrey M.·2009·Development
DOI 10.1242/dev.038315PMC PMC2709066
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Abstract

Although purines and purinergic signaling are crucial for numerous biochemical and cellular processes, their functions during vertebrate embryonic development have not been well characterized. We analyze two recessive zebrafish mutations that affect de novo purine synthesis, gart and paics. gart encodes phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase,phosphoribosylaminoimidazole synthetase, a trifunctional enzyme that catalyzes steps 2, 3 and 5 of inosine monophosphate (IMP) synthesis. paicsencodes phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase, a bifunctional enzyme that catalyzes steps 6 and 7 of this process. Zygotic gart and paics mutants have pigmentation defects in which xanthophore and iridophore pigmentation is almost completely absent, and melanin-derived pigmentation is significantly decreased, even though pigment cells are present in normal amounts and distributions. Zygotic gart and paics mutants are also microphthalmic, resulting from defects in cell cycle exit of proliferative retinoblasts within the developing eye. Maternal-zygotic and maternal-effect mutants demonstrate a crucial requirement for maternally derived gartand paics; these mutants show more severe developmental defects than their zygotic counterparts. Pigmentation and eye growth phenotypes in zygotic gart and paics mutants can be ascribed to separable biosynthetic pathways: pigmentation defects and microphthalmia result from deficiencies in a GTP synthesis pathway and an ATP synthesis pathway,respectively. In the absence of ATP pathway activity, S phase of proliferative retinoblasts is prolonged and cell cycle exit is compromised, which results in microphthalmia. These results demonstrate crucial maternal and zygotic requirements for de novo purine synthesis during vertebrate embryonic development, and identify independent functions for ATP and GTP pathways in mediating eye growth and pigmentation, respectively.

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Cited by

Sorted by citations

Authors
Ng, A., Uribe, R. A., Yieh, L., Nuckels, R., & Gross, J. M.
Affiliations
The University of Texas at Austin (US)
ORCID
Venue
Development
Publisher
The Company of Biologists
Published
2009-08-01
Volume
136
Issue
15
Pages
2601-2611
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
DOI
10.1242/dev.038315
PMC
PMC2709066
OpenAlex
W1972806235
Cited by
87
References
0
Citations by year
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FWCI
1.12
Type
journal article
Language
en
Open access
Locations
  • Development (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Eye Institute (R01EY018005, F31EY019239)
  • National Center for Research Resources (P40RR012546)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
Keywords
de novo purine synthesis, GART, PAICS, pigmentation, melanin, microphthalmia, cell cycle exit, ATP production, purinergic signaling, embryonic development
MeSH terms
Adenosine Triphosphate, Animals, Carboxy-Lyases, Embryo, Nonmammalian, Eye, Female, Guanosine Triphosphate, Inosine Monophosphate, Microphthalmos, Models, Biological, Mutation, Peptide Synthases, Phenotype, Pigmentation, Pigments, Biological, Purines, Retina, Zebrafish, S Phase, Apoptosis, Gene Expression Regulation, Developmental, Zebrafish Proteins, Embryonic Development, Cell Proliferation, Phosphoribosylglycinamide Formyltransferase

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