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The bHLH transcription factor Olig2 is required for sequential cell fate determination of both motor neurons and oligodendrocytes and for progenitor proliferation in the central nervous system. However, the role of Olig2 in peripheral sensory neurogenesis remains unknown. We report that Olig2 is transiently expressed in the newly differentiated olfactory sensory neurons (OSNs) and is down-regulated in the mature OSNs in mice from early gestation to adulthood. Genetic fate mapping demonstrates that Olig2-expressing cells solely give rise to OSNs in the peripheral olfactory system. Olig2 depletion does not affect the proliferation of peripheral olfactory progenitors and the fate determination of OSNs, sustentacular cells, and the olfactory ensheathing cells. However, the terminal differentiation and maturation of OSNs are compromised in either Olig2 single or Olig1/Olig2 double knockout mice, associated with significantly diminished expression of multiple OSN maturation and odorant signaling genes, including Omp, Gnal, Adcy3, and Olfr15. We further demonstrate that Olig2 binds to the E-box in the Omp promoter region to regulate its expression. Taken together, our results reveal a distinctly novel function of Olig2 in the periphery nervous system to regulate the terminal differentiation and maturation of olfactory sensory neurons.

Oligodendrocytes, a type of glial cell in the central nervous system, have a critical role in the formation of myelin around axons, facilitating saltatory conduction, and maintaining the integrity of nerve axons. The dysregulation of oligodendrocyte differentiation and homeostasis have been implicated in a wide range of neurological diseases, including dysmyelinating disorders (e.g., Pelizaeus‐Merzbacher disease), demyelinating diseases (e.g., multiple sclerosis), Alzheimer's disease, and psychiatric disorders. Therefore, unraveling the mechanisms of oligodendrocyte development, differentiation, and homeostasis is essential for understanding the pathogenesis of these diseases and the development of therapeutic interventions. Numerous studies have identified and analyzed the functions of transcription factors, RNA metabolic factors, translation control factors, and intracellular and extracellular signals involved in the series of processes from oligodendrocyte fate determination to terminal differentiation. DEAD‐box proteins, multifunctional RNA helicases that regulate various intracellular processes, including transcription, RNA processing, and translation, are increasingly recognized for their diverse roles in various aspects of oligodendrocyte development, differentiation, and maintenance of homeostasis. This review introduces the latest insights into the regulatory networks of oligodendrocyte biology mediated by DEAD‐box proteins. [ABSTRACT FROM AUTHOR]

The Vps13a gene encodes a lipid transfer protein called VPS13A, or chorein, associated with mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), mitochondria–endosomes, and lipid droplets. This protein plays a crucial role in inter-organelle communication and lipid transport. Mutations in the VPS13A gene are implicated in the pathogenesis of chorea-acanthocytosis (ChAc), a rare autosomal recessive neurodegenerative disorder characterized by chorea, orofacial dyskinesias, hyperkinetic movements, seizures, cognitive impairment, and acanthocytosis. Previous mouse models of ChAc have shown variable disease phenotypes depending on the genetic background. In this study, we report the generation of a Vps13a flox allele in a pure C57BL/6N mouse background and the subsequent creation of Vps13a knockout (KO) mice via Cre-recombination. Our Vps13a KO mice exhibited increased reticulocytes but not acanthocytes in peripheral blood smears. Additionally, there were no significant differences in the GFAP- and Iba1-positive cells in the striatum, the basal ganglia of the central nervous system. Interestingly, we observed abnormal spermatogenesis leading to male infertility. These findings indicate that Vps13a KO mice are valuable models for studying male infertility and some hematological aspects of ChAc. [ABSTRACT FROM AUTHOR]

In the present study, we examined neural circuit formation in the forebrain of the Olig2 knockout (Olig2‐KO) mouse model and found disruption of the anterior commissure at the late foetal stage. Axon bundles of the anterior commissure encountered the wall of the third ventricle and ceased axonal extension. L1‐CAM immunohistochemistry showed that Olig2‐KO mice lose decussation formation in the basal forebrain. DiI tracing revealed that the thin bundles of the anterior commissure axons crossed the midline but ceased further extension into the deep part of the contralateral side. Furthermore, some fractions of DiI‐labelled axons were oriented dorsolaterally, which was not observed in the control mouse forebrain. The rostral part of the third ventricle was much wider in the Olig2‐KO mice than in wild‐type mice, which likely resulted in the delay of midline fusion and subsequent delay and malformation of the anterior commissure. We analysed gene expression alterations in the Olig2‐KO mice using a public database and found multiple genes, which are related to axon guidance and epithelial‐mesenchymal transition, showing subtle expression changes. These results suggest that Olig2 is essential for anterior commissure formation, likely by regulating multiple biological processes. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2008.06.001 Byline: Katsuhiko Ono (a)(b), Hirohide Takebayashi (a)(b), Kazuyo Ikeda (a)(c), Miki Furusho (a)(b), Takumi Nishizawa (a)(b), Keisuke Watanabe (a)(b), Kazuhiro Ikenaka (a)(b) Keywords: Cre/loxP; Tamoxifen; Astrocyte; Oligodendrocyte; GABAergic neuron; Glutamatergic neuron Abstract: Olig2 is a basic helix-loop-helix transcription factor essential for oligodendrocyte and motoneuron development in the spinal cord. Olig2-positive (Olig2+) cells in the ventricular zone of the ventral telencephalon have been shown to differentiate into GABAergic and cholinergic neurons. However, the fate of Olig2 lineage cells in the postnatal forebrain has not been fully described and Olig2 may regulate the development of both astrocytes and oligodendrocytes. Here, we examined the fate of embryonic Olig2+ progenitors using a tamoxifen-inducible Cre/loxP system. Using long-term lineage tracing, Olig2+ cells in the early fetal stage primarily differentiated into GABAergic neurons in the adult telencephalon, while those in later stages gave rise to macroglial cells, both astrocytes and oligodendrocytes. Olig2+ progenitors in the diencephalon developed into oligodendrocytes, as observed in the spinal cord, and a fraction developed into glutamatergic neurons. Olig2 lineage oligodendrocytes tended to form clusters, probably due to local proliferation at the site of terminal differentiation. In spite of the abundance of Olig2 lineage GABAergic neurons in the normal neocortex, GABAergic neurons seemed to develop at normal density in the Olig2 deficient mouse. Thus, Olig2 is dispensable for GABAergic neuron specification. In contrast, at the late fetal stage in the Olig2 deficient mouse, astrocyte development was retarded in the dorsal neocortex, but not in the basal forebrain. Olig2 functions, therefore, in gliogenesis in the dorsal pallium. Short-term lineage tracing experiments revealed that the majority of late Olig2+ cells were not direct descendants of early Olig2+ progenitors in the fetal forebrain. These observations indicate that embryonic Olig2+ progenitor cells change their differentiative properties during development, and also that Olig2 plays a role in astrocyte development in a region-specific manner. Author Affiliation: (a) Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan (b) Department of Physiological Sciences, School of Life Science, The Graduate University of Advanced Studies (Sokendai), Miki-cho, Kanagawa 240-0193, Japan (c) Third Department of Internal Medicine, Kagawa University School of Medicine, Kagawa 761-0793, Japan Article History: Received 24 October 2007; Revised 19 May 2008; Accepted 2 June 2008

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2006.01.031 Byline: Miki Furusho (a)(b), Katsuhiko Ono (a)(b), Hirohide Takebayashi (b), Noritaka Masahira (b)(c), Tetsushi Kagawa (d), Kazuyo Ikeda (b)(e), Kazuhiro Ikenaka (a)(b) Keywords: Tamoxifen; Cre-mediated recombination; LacZ; EGFP; Choline acetyltransferase; In situ hybridization; BrdU; Lhx8 Abstract: Cholinergic neurons, which express choline acetyltransferase (ChAT), are a major neuron subset generated in the basal forebrain. Areas presumed to be sites of origin of cholinergic neurons are roughly demarcated by expression of Olig2, a basic helix-loop-helix transcription factor, which includes the medial ganglionic eminence, septal area, and anterior entopeduncular/preoptic area. In the present study, we examined the involvement of Olig2 in cholinergic differentiation. When the Olig2-expressing cells at E12.5 were permanently modified to express the lacZ or EGFP gene by tamoxifen-induced Cre-mediated recombination, the cells marked by reporter gene expression were widely distributed in the basal forebrain by E18.5, some of which expressed neuronal markers. We showed that a small number of cells were double-positive for ChAT and X-gal or EGFP in almost all cases. In addition, the number of ChAT+ cells was reduced to 60% in the Olig2 knockout mouse basal forebrain. No evidence of elevated apoptosis or reduced proliferation was observed in the knockout mouse forebrain. The present study provides the first direct evidence for involvement of the Olig2 gene in cholinergic differentiation in the basal forebrain. Author Affiliation: (a) Department of Physiological Sciences, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi 444-8787, Japan (b) Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Aichi 444-8787, Japan (c) Department of Neurosurgery, Kochi Medical School, Nankoku, Kochi 783-8505, Japan (d) Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan (e) Third Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa 761-0793, Japan Article History: Received 24 May 2005; Revised 27 January 2006; Accepted 30 January 2006

Origin of motoneurons and oligodendrocytes from Olig2 positive progenitors is discussed. Other astrocytes that are originating from pMN domain are presented.

In the developing spinal cord, oligodendrocyte progenitors (OLPs) originate from the ventral neuroepithelium and the specification of this lineage depends on the inductive activity of Sonic hedgehog (Shh) produced by ventral midline cells. On the other hand, it has been shown that OLP identity is acquired by the coexpression of the transcription factors olig2 and nkx2.2. Although initially expressed in adjacent nonoverlapping domains of the ventral neuroepithelium, these transcription factors become coexpressed in the pMN domain at the time of OLP specification through dorsal extension of the Nkx2.2 domain. Here we show that Shh is sufficient to promote the coexpression of Olig2 and Nkx2.2 in neuroepithelial cells. In addition, Shh activity is necessary for this coexpression since blocking Shh signalling totally abolishes Olig2 expression and impedes dorsal extension of Nkx2.2. Although Shh at these stages affects neuroepithelial cell proliferation, the dorsal extension of the Nkx2.2 domain is not due to progenitor proliferation but to repatterning of the ventral neuroepithelium. Finally, Shh not only stimulates OLP specification but also simultaneously restricts the ventral extension of the astrocyte progenitor (AP) domain and reduces astrocyte development. We propose that specification of distinct glial lineages is the result of a choice that depends on Shh signalling. Keywords: Oligodendrocyte; Astrocyte; Sonic hedgehog; Spinal cord; Chick embryo; Oils2; Nkx2.2

The salivary system in mammals is comprised of three independently developed pairs of organs, the parotid, submaxillar, and sublingual glands. Each gland is composed of various ductal and acinar cell types that fulfill multiple roles. However, the molecular mechanisms regulating their biogenesis and functions are still largely unknown. In this paper, we report that two class B basic helix-loop-helix (bHLH) transcriptional regulators delineate the ductal and the acinar cells in salivary glands. Sgn1, a novel class B bHLH factor, is specifically expressed in the salivary duct cells, while the acinar cellsare characterized by the expression of another class B bHLH factor, Mist1. The molecular nature of Sgn1 was also investigated: it binds to specific sequences of DNA as a dimer with a class A bHLH factor and acts as a negative transcriptional regulator against other bHLH factors. This study provides an important cue towards better understanding of the generation and function of multiple cell types in salivary glands. In addition, Sgn1 expression exhibits a reverse relationship with the development of male phenotypes, suggesting its role in gender dimorphism in the salivary glands. Key Words: mouse; salivary glands; basic helix-loop-helix (bHLH); transcription factor; Sgn1; Mist1.