Abstract
The NR4A orphan nuclear receptor, Nurr1, has been shown to regulate the expression of osteoblastic genes and osteoblastic differentiation. However, the expression profile of Nurr1 in the developing mouse forelimb and its relationship to skeletogenesis has not, to the best of our knowledge, been previously analyzed. In this study, the relationship between Nurr1 expression pattern, skeletogenesis and osteogenesis in the developing mouse forelimb was investigated. The expression level of Nurr1 during development was also quantified by real time-polymerase chain reaction. Our results revealed that Nurr1 is expressed in the mesenchyme cells that will form the skeleton. Nurr1 is aabundantly expressed in the primary ossification centers of the forelimb skeletal elements and its expression level is gradually increased during limb development, particularly, at the onset of ossification. Collectively, these data suggested that Nurr1 plays an important role in skeletogenesis and patterning of the developing mouse forelimb.
Highlights
Nuclear Receptors (NRs) are DNA binding transcription factors that possess conservative domain organization and control key metabolic and developmental pathways
In the newly formed osteoid matrix around the ossification region in the central diaphyseal area, osteoblasts become ovoid in shape and are completely surrounded by a lacunae filled with matrix forming definite osteocytes (Fig. 2C).Numerous vascular tissues are noticed in the primary ossification center
NR4A receptors lack identified natural ligands and as they are encoded by immediate early genes it is plausible that an important mechanism regulating their activities is to regulate their expression levels
Summary
Nuclear Receptors (NRs) are DNA binding transcription factors that possess conservative domain organization and control key metabolic and developmental pathways. They are one of the most abundant classes of transcriptional regulators in metazoan animals. NRs provide direct control of gene expression via various extracellular and intracellular signals. These receptors are subdivided into several subfamilies according to similarities of amino acid sequences and some other properties (Smirnov, 2002). Most of these subfamilies are ligand-inducible transcription factors mediating the effects of small lipophilic ligands such as steroid hormones, retinoids, thyroid hormones and vitamin D. There are a large number of NRs lacking identified physiological ligands and are referred to as orphan nuclear receptors (Giguére, 1999)
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