Development of the Pteridine Pathway in the Zebrafish,Danio rerio

Abstract

In the zebrafish, the peripheral neurons and the pigment cells are derived from the neural crest and share the pteridine pathway, which leads either to the cofactor tetrahydrobiopterin or to xanthophore pigments. The components of the pteridine pattern were identified as tetrahydrobiopterin, sepiapterin, 7-oxobiopterin, isoxanthopterin, and 2,4,7-trioxopteridine. The expression of GTP cyclohydrolase I activity during the first 24-h postfertilization, followed by 6-pyruvoyl-5,6,7,8-tetrahydropterin synthase and sepiapterin reductase, suggest an early supply of tetrahydrobiopterin for neurotransmitter synthesis in the neurons and for tyrosine supply in the melanophores. At 48-h postfertilization, sepiapterin formation branches off the de novo pathway of tetrahydrobiopterin synthesis. Sepiapterin, via 7,8-dihydrobiopterin and biopterin, serves as a precursor for the formation of 7-oxobiopterin, which may be further catabolized to isoxanthopterin and 2,4,7-trioxopteridine. Neither 7,8-dihydrobiopterin nor biopterin is a substrate for xanthine oxidoreductase. In contrast, both of these compounds are oxidized at C-7 by a xanthine oxidase variant form, which is inactivated by KCN, but is insensitive to allopurinol. The oxidase and the dehydrogenase form of xanthine oxidoreductase as well as the xanthine oxidase variant have specific developmental patterns. It follows that GTP cyclohydrolase I, the formation of sepiapterin, and the xanthine oxidoreductase family control the pteridine pathway in the zebrafish.

The zebrafish mutation m865 affects formation of dopaminergic neurons and neuronal survival, and maps to a genetic interval containing the sepiapterin reductase locus

“…spr-expression in zebrafish was shown in melanocytes in head and trunk region. This is consistent with the a role in BH4 synthesis, which is, in addition to its role in neurotransmitter synthesis, the supply with tyrosine for melanogenesis, (Ziegler et al 2000;Pelletier et al 2001). The partial colocalization of zebrafish sprexpression (retina, diencephalon, midbrain-hindbrain boundary, cerebellum) with regions of morphological malformation in the m865 mutant embryo further supports the classification of spr as an important candidate gene for the mutation in m865.…”

Expression of one isoform of GTP cyclohydrolase I coincides with the larval black markings of the swallowtail butterfly, Papilio xuthus

“…Both TH and PAH require BH 4 as a cofactor, and we expected that the overall expression of GTPCHI and its downstream pathways in epidermis could be appropriate both for the uniformly expressed PAH and the marking-specifically expressed TH to receive BH 4 . GTPCHI activity is necessary for not only the synthesis of catecholamine, a precursor of melanin but also pteridines-related pigments (Takahashi and Nakagoshi, 1994;Ziegler et al, 2000). BH 4 is also an essential cofactor for nitric oxide synthase (Marletta, 1993;Imamura et al, 2002).…”

Genetic Linkage and Color Polymorphism in the Southern Platyfish (Xiphophorus maculatus): A Model System for Studies of Color Pattern Evolution

“…Both are known to contribute to eye coloration in fishes, 39 and fish are known to synthesize both types of pigments. 40 Two codominant alleles have been described for eye coloration, one of which produces a dense yellow iris (Iy) and the other a red iris (Ir). Likely pigment cell candidates for these color patterns are biochromes containing red or yellow carotenoids, biochromes containing red or yellow purines, or biochromes containing both types of pigments, all of which are found to affect eye coloration in fishes.…”