Zebrafish ftz-f1a (nuclear receptor 5a2) functions in skeletal muscle organization

Abstract

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.

A systematic analysis of the skeletal muscle miRNA transcriptome of chicken varieties with divergent skeletal muscle growth identifies novel miRNAs and differentially expressed miRNAs

“…However, analysis of their targets demonstrated that several were involved in myogenesis regulation, suggesting that these miRNAs could participate in regulating muscle development through their target genes. For example, miR-200b has eight predicted targets, among which are three genes RECK, SLC38A2 and Nr5a2 , which encode proteins that are reported to be involved in muscle development [51-53]. …”

“…Nr5a2 is the putative target of gga-miR-200b, gga-miR-128 and gga-miR-27b. Its product, the nuclear receptor transcription factor Nr5a2, has been reported to function during skeletal muscle organization [53]. Therefore, although little is known about the specific functions of several of these miRNAs (e.g.…”

The differentiation and morphogenesis of craniofacial muscles

“…At this stage, endothelial cells stream into the previously avascular muscle primordium (Ruberte et al, 2002). While a few participating molecules are known (Sheela et al, 2005), the molecular basis for these alignments and separations is not known.…”

Structure-based Discovery of Antagonists of Nuclear Receptor LRH-1

“…Because of its decisive role in cell differentiation, LRH-1 is linked to multiple developmental pathways, including Hedgehog (8) and Wnt/␤-catenin (6,9,10) signaling. In particular, LRH-1 enhances transcription of multiple genes controlled by the regulatory Wnt/␤-catenin cascade.…”