Steroidogenic factor 1 (SF-1 or NR5A1), is a Ftz-F1 member of the nuclear receptor superfamily that plays essential roles in endocrine development, steroidogenesis, and gonad differentiation. We investigated modifications that control SF-1 function and found that SF-1 could be conjugated by SUMO-1 both in vitro and in vivo. Wild-type but not conjugation-deficient SF-1 was localized at the nuclear speckles together with SUMO-1. Thus, SUMO-1 conjugation could also target SF-1 into nuclear speckles. Collectively, these results suggest that SUMO modification at the repression domains targets SF-1 to nuclear speckles; this could be an important mechanism by which SF-1 is regulated. SF-1 was modified predominantly at

Fushi tarazu factor 1 (Ftz-F1, NR5A) is a zinc-finger transcription factor that belongs to the nuclear receptor superfamily and regulates genes that are involved in sterol and steroid metabolism in gonads, adrenals, liver and other tissues. To understand the evolutionary origins and developmental genetic relationships of the Ftz-F1 genes, we have cloned four homologous Ftz-f1 genes in zebrafish, called ff1a, ff1b, ff1c and ff1d. These four genes have different temporal and spatial expression patterns during development, indicating that they have distinct mechanisms of genetic regulation. Among them, the ff1a expression pattern is similar to mammalian Nr5a2, while the ff1b pattern is similar to that of mammalian Nr5a1. Genetic mapping experiments show that these four ff1 genes are located on chromosome segments conserved between the zebrafish and human genomes, indicating a common ancestral origin. Phylogenetic and conserved synteny analysis show that ff1a is the orthologue of NR5A2, and that ff1b and ff1d genes are co-orthologues of NR5A1 that arose by a gene-duplication event, probably a whole-genome duplication, in the ray-fin lineage, and each gene is located next to an NR6A1 co-orthologue as in humans, showing that the tandem duplication occurred before the divergence of human and zebrafish lineages. ff1c does not have a mammalian counterpart. Thus we have characterized the phylogenetic relationships, expression patterns and chromosomal locations of these Ftz-F1 genes, and have demonstrated their identities as NR5A genes in relation to the orthologous genes in other species.

Fushi-tarazu factor 1a (Ftz-F1a, Ff1a, Nr5a2) is a nuclear receptor with diverse functions in many tissues. Here, we report the function of ff1a in zebrafish muscle differentiation. In situ hybridization revealed that ff1a mRNA was present in the adaxial and migrating slow muscle precursors and was down-regulated when slow muscle cells matured. This expression was under the control of hedgehog genes, expanded when hedgehog was increased and missing in mutants defective in genes in the Hedgehog pathway like you-too (yot), sonic you (syu), and u-boot (ubo). Blocking ff1a activity by injecting a deleted form of ff1a or an antisense ff1a morpholino oligo into fish embryos caused thinner and disorganized fibers of both slow and fast properties. Transient expression of ff1a in syu, ubo, and yot embryos led to more fibril bundles, even when slow myoblasts were transfated into fast properties. We showed that ff1a and prox1 complemented each other in slow myofibril assembly, but they did not affect the expression of each other. These results demonstrate that ff1a functions in both slow and fast muscle morphogenesis in response to Hedgehog signaling, and this function parallels the activity of another slow muscle gene, prox1.