Biochemical and Biophysical Research Communications
Osterix is dispensable for the development of the mouse olfactory bulb
Introduction
The olfactory bulb is an important organ, which detects odorants via complex pathways, and is divided into the main olfactory bulb and the accessory olfactory bulb [1]. The main olfactory bulb has a function for odor recognition and discrimination, detecting odorants at the olfactory epithelium. It consists of five layers between the rostral and caudal surfaces: the glomerular layer, the external plexiform layer, the mitral cell layer (MCL), the inner plexiform layer, and the granule cell layer (GCL). Most granule cells in the GCL are GABAergic inhibitory interneurons [2] and the mitral cells in the MCL are closely related to projection neurons. Few studies have been performed to evaluate the olfactory bulb compared to those conducted for other organs, and various genes expressed in the olfactory bulb are still being identified.
Interneurons, which are located in the olfactory bulb, have major functions in adult neurogenesis. They are regulated by transcription factors, growth factors, neurotransmitters, and environmental factors, which play a role in cell migration, differentiation, and maturation. Several factors also contribute to olfactory bulb maturation at the embryonic stage. Fibroblast growth factor/fibroblast growth factor receptor 1 signaling is necessary for olfactory bulb morphogenesis [3]. Pax6 is expressed in dopaminergic and GABAergic periglomerular cells [4], [5], and assists in embryonic olfactory interneuron formation [6]. Dlx1 and Dlx2 transcription factors are also characterized in GABAergic interneurons, to promote cell differentiation, migration, and survival [7]. Runx2 and Osterix (Osx) are known to be osteoblast-specific transcription factors for bone formation [8], [9]. Runx2 has a positive function in the differentiation of osteoblasts and hypertrophic chondrocytes [8], and Osx plays a role in differentiating chondrocytes, perichondrium, and osteoblasts in bone [9]. Although they are essential to skeletal tissues, several studies have shown that Runx2 and Osx are expressed in non-skeletal tissues, including brain, offering evidence of their novel functions in organs other than bone [10], [11], [12]. Recently, it has been reported that Osx is strongly expressed from the glomerular layer to the superficial GCL of the olfactory bulb, compared with minimal expression in the cerebral cortex and cerebellum, in mice [12]. Interestingly, Osx-positive cells are located in mature interneurons of the GCL, suggesting that Osx may have another function as a marker for mature neuroblasts in the olfactory bulb. However, its function in the olfactory bulb has not been well investigated. In this study, an Osx-deficient mouse model was analyzed for the first time in order to find out whether the organizational alteration of the olfactory bulb is due to changes in Osx expression.
Section snippets
Animal preparation
All animal experiments were conducted with the approval of Kyungpook National University. Osx heterozygous mice were kindly provided by Dr. Benoit de Crombrugghe (University of Texas M. D. Anderson Cancer Center, USA) [9]. To produce Osx-null mutant embryos, male Osx heterozygous mice were crossed with female Osx heterozygous mice. Genomic DNA was isolated from mouse embryos or tails, and PCR genotyping was conducted using 100 ng of isolated genomic DNA. Reactions for PCR amplifications were
No morphological difference between the olfactory bulb in wild-type and Osx heterozygous mice at postnatal stage
Osx is known as a transcription factor that has a function in bone formation and osteoblast differentiation in mice [9]. Sp7, the human Osx gene, also contribute to skeletogenesis [13]. In addition to expression in bone, Sp7 is expressed in non-skeletal tissues including the brain, placenta, lung, ovary, and testis [13]. However, its function in non-skeletal tissues has not yet been studied. Recently, in vivo Osx expression has been observed in the mouse olfactory bulb for the first time [12].
Acknowledgements
This Research was supported by the Kyungpook National University Research Fund 2014 (J.E. Kim) and the Health Fellowship Foundation (G.I. Park).
References (13)
- et al.
Subtype-specific reduction of olfactory bulb interneurons in Pax6 heterozygous mutant mice
Neurosci. Res.
(2009) - et al.
Generation of Cre-transgenic mice using Dlx1/Dlx2 enhancers and their characterization in GABAergic interneurons
Mol. Cell. Neurosci.
(2009) - et al.
Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts
Cell
(1997) - et al.
The novel zinc finger-containing transcription factor Osterix is required for osteoblast differentiation and bone formation
Cell
(2002) - et al.
Transactivation by Runt related factor-2 of matrix metalloproteinase-13 in astrocytes
Neurosci. Lett.
(2009) - et al.
In vivo expression of Osterix in mature granule cells of adult mouse olfactory bulb
Biochem. Biophys. Res. Commun.
(2011)
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