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. paics encodes 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 gart and 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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BACKGROUND AND OBJECTIVES: Describe the financial burden and worry that families of preterm infants experience after discharge from the neonatal intensive care unit (NICU). METHODS: We surveyed 365 parents of preterm infants in a cross-sectional study regarding socio-demographics, supplemental security income (SSI), and financial worry. We completed a multivariable logistic regression model to examine the adjusted association of financial worry with modifiable factors. RESULTS: We found that 53% of participants worried about healthcare costs after NICU discharge. After adjusting for sociodemographic and infant characteristics, we identified that, aOR (95% CI), out-of-pocket costs from the NICU index hospitalization, 3.51 (1.7, 7.26) and durable medical equipment use, 2.41 (1.11, 5.23) was associated with increased financial worry while enrollment in SSI, 0.38 (0.19, 0.76) was associated with decreased financial worry. CONCLUSIONS: We identified factors that could contribute to financial burden after NICU discharge that may advise future work to target financial support systems.