Gene Duplication of Zebrafish JAK2 Homologs Is Accompanied by Divergent Embryonic Expression Patterns: Only jak2a Is Expressed During Erythropoiesis

Abstract

Members of the JAK family of protein tyrosine kinase (PTK) proteins are required for the transmission of signals from a variety of cell surface receptors, particularly those of the cytokine receptor family. JAK function has been implicated in hematopoiesis and regulation of the immune system, and recent data suggest that the vertebrate JAK2gene may play a role in leukemia. We have isolated and characterizedjak cDNAs from the zebrafish Danio rerio. The zebrafish genome possesses 2 jak2 genes that occupy paralogous chromosome segments in the zebrafish genome, and these segments conserve syntenic relationships with orthologous genes in mammalian genomes, suggesting an ancient duplication in the zebrafish lineage. The jak2a gene is expressed at high levels in erythroid precursors of primitive and definitive waves and at a lower level in early central nervous system and developing fin buds. jak2b is expressed in the developing lens and nephritic ducts, but not in hematopoietic tissue. The expression of jak2a was examined in hematopoietic mutants and found to be disrupted in clocheand spadetail, suggesting an early role in hematopoiesis. Taken together with recent gene knockout data in the mouse, we suggest that jak2a may be functionally equivalent to mammalianJak2, with a role in early erythropoiesis.

Zebrafish stat3 is expressed in restricted tissues during embryogenesis and stat1 rescues cytokine signaling in a STAT1‐deficient human cell line

“…6a). A subset of these structures, the trigeminal and the posterior lateral line ganglia, also expresses the cytoplasmic kinase jak1 (Oates et al, 1999) at this stage (Fig. 6b).…”

“…With an overall identity of 63.9% to mouse Stat1, the zebrafish stat1 protein is significantly more diverged than the paralogous stat3, which displays an overall identity to mouse Stat3 of 86.5%. By comparison, the jak2 proteins of zebrafish are approximately 65% identical to their mouse homolog (Oates et al, 1999). Phylogenetic analysis of all known STAT1 and STAT3 genes indicates that the STAT3 gene appears to be evolving 2.5 times slower than STAT1 in both fish and mammalian lineages ( Fig.…”

“…Alternatively, there may exist additional stat3 homologs in the zebrafish that have retained a blood-specific expression pattern. In this regard, it is noted that there are two JAK2 homologs in the zebrafish, only one of which is ex- pressed in erythroblasts (Oates et al, 1999). stat3 expression in head mesenchyme of the pharyngeal arches is not evident in the zebrafish till 3 dpc; this contrasts with an early (E 9.5) Stat3 expression at high level in head mesenchyme in the mouse embryo; however, in the mouse, the expression does not appear to be restricted to the pharyngeal arches (Duncan et al, 1997).…”

“…In rat cortical and spinal neuron precursor cells, Stat1 and Stat3 are rapidly phosphorylated in response to CNTF and bind to a functionally critical SBE in the promoter of the astrocyte specific GFAP gene; furthermore, a dominant negative Stat3 isoform suppresses the CNTF differentiation activity (Bonni et al, 1997). In the zebrafish, the JAK/STAT pathway may play an analogous role in CNS development, and the expression of stat1 and stat3 (as well as jak1 and jak2a, Oates et al, 1999) in regions of the developing zebrafish CNS is consistent with this notion. In this study, we demonstrate the expression of stat3 in cranial motor nuclei in the midbrain and hindbrain from day 3 onward.…”

“…Embryos raised to time points beyond 24 hr postfertilization (hpf) were transferred to E3 embryo medium with 0.003% phenylthiourea (PTU, Sigma) to prevent melanization. Riboprobe synthesis and in situ hybridization were conducted essentially as described (Shulte-Merker et al, 1992) with modifications as in Oates et al (1999). Furthermore, an increased stringency was afforded by hybridization and washes with 0.05ϫ SSC at 70°C.…”