Takanori Wakaoka

Tracing Sox10-expressing cells elucidates the dynamic development of the mouse inner ear.

The inner ear is constituted by complicated cochlear and vestibular compartments, which are derived from the otic vesicle, an embryonic structure of ectodermal origin. Although the inner ear development has been analyzed using various techniques, the developmental events have not been fully elucidated because of the intricate structure. We previously developed a Sox10-IRES-Venus mouse designed to express green fluorescent protein under the control of the Sox10 promoter. In the present study, we showed that the Sox10-IRES-Venus mouse enabled the non-destructive visualization and understanding of the morphogenesis during the development of the inner ear. The expression of the transcription factor Sox10 was first observed in the invaginating otic placodal epithelium, and continued to be expressed in the mature inner ear epithelium except for the hair cells and mesenchymal cells. We found that Sox10 was expressed in immature hair cells in the developing inner ear, suggesting that hair cells were generated from the Sox10-expressing prosensory cells. Furthermore, we demonstrated that scattered Sox10-expressing cells existed around the developing inner ear, some of which differentiated into pigmented melanocytes in the stria vascularis, suggesting that they were neural crest cells. Further analyzing the Sox10-IRES-Venus mice would provide important information to better understand the development of the inner ear.

Neural crest‐derived cells sustain their multipotency even after entry into their target tissues

Background: Neural crest cells (NC cells) are highly migratory multipotent cells. Their multipotency is transient at the early stage of their generation; soon after emerging from the neural tube, these cells turn into lineage‐restricted precursors. However, recent studies have disputed this conventionally believed paradigm. In this study, we analyzed the differentiation potency of NC‐derived cells after their arrival at target tissues. Results: Using Sox10‐IRES‐Venus mice, we found that the NC‐derived cells in the skin, DRG, and inner ear could be divided into two populations: Sox10‐positive/Kit‐negative cells (Sox10+/Kit‐ cells) and Sox10‐ and Kit‐positive cells (Sox10+/Kit+ cells). Only the Sox10+/Kit‐ cells were detected in the intestines. Unexpectedly, the Sox10+/Kit+ cells differentiated into neurons, glial cells, and melanocytes, showing that they had maintained their multipotency even after having entered the target tissues. The Sox10+/Kit+ cells in the DRG maintained their multipotency for a restricted period during the earlier embryonic stages, whereas those in the skin and inner ear were multipotent yet even in later embryonic stages. Conclusions: We showed that NC‐derived Sox10+/Kit+ cells maintained their multipotency even after entry into the target tissues. This unexpected differentiation potency of these cells in tissues seems to have been strictly restricted by the tissue microenvironment. Developmental Dynamics 243:368–380, 2014.

Damping control of balance in the medial/lateral direction and the risk of falling in the elderly.

Aims:  A proportional–integral–derivative (PID) control has recently been used as a control algorithm of body balance. The purpose of this study was to elucidate an association of the proportional and derivative gain based on the PID control gain for balance for quiet standing with the risk factor for falls in the elderly.

Dual origin of melanocytes defined by Sox1 expression and their region-specific distribution in mammalian skin

Melanocytes are pigment‐producing cells generated from neural crest cells (NCCs) that delaminate from the dorsal neural tube. The widely accepted premise that NCCs migrating along the dorsolateral pathway are the main source of melanocytes in the skin was recently challenged by the finding that Schwann cell precursors are the major cellular source of melanocytes in the skin. Still, in a wide variety of vertebrate embryos, melanocytes are exclusively derived from NCCs. In this study, we show that a NCC population that is not derived from Sox1+ dorsal neuroepithelial cells but are derived from Sox1− cells differentiate into a significant population of melanocytes in the skin of mice. Later, these Sox1− cells clearly segregate from cells that originated from Sox1+ dorsal neuroepithelial cell‐derived NCCs. The possible derivation of Sox1− cells from epidermal cells also strengthens their non‐neuroepithelial origin.

The association between impaired perception of verticality and cerebral white matter lesions in the elderly patients with orthostatic hypotension.

BACKGROUND The morbidity of orthostatic hypotension (OH) increases with aging and the elderly often complain of dizziness associated with OH, which is implicated in white matter lesions (WMLs) on MRI. However little is known how WMLs are contributed to the development of dizziness in elderly patients. OBJECTIVE We evaluated the involvement of cerebral WMLs in the vertical perception in the elderly with OH. METHODS This study consisted of 71 dizzy patients who underwent the examinations including the Schellong orthostatic test and subjective visual vertical (SVV) test. RESULTS The male patients aged <65 years with OH (1.9 ± 0.9°) showed a significantly higher magnitude of variance of SVV, which reflects an impaired vertical perception, in comparison with the male patients aged <65 years without OH and the male patients aged < 65 years with OH (1.0 ± 0.4°, 0.9 ± 0.4°, p < 0.05). The variance of SVV significantly correlated with the volume of WMLs in both sides on MRI in the male, but not female patients (p < 0.01). CONCLUSIONS Our results suggest that severe WMLs in the elderly with OH are involved in impaired perception of verticality, resulting in inducing subjective dizziness.

Galectin-1 enhances the generation of neural crest cells

Neural crest (NC) cells are multipotent cells that emerge from the dorsal region of the neural tube. After delaminating from the neural tube, NC cells migrate throughout the developing embryo and differentiate into various cells: neurons and glial cells of the peripheral nervous system, melanocytes of skin, and skeletal elements of the face and head. We previously analyzed the gene expression profile of a NC subpopulation isolated from Sox10-IRES-Venus mice and found that the carbohydrate-binding protein, Galectin-1 (Gal-1) was strongly expressed in generating NC cells. In the present study, we identified GAL-1 as a factor that promotes NC cell generation. Gal-1 was significantly expressed in NC cells generated in explanted neural tubes. The presence of GAL-1 enhanced the generation of NC-like cells from mouse embryonic stem (ES) cells. In the differentiation of ES cells into NC-like cells, GAL-1 enhanced neurogenesis in the early stages and facilitated NC-like cell generation in the later stages. GAL-1 also enhanced the generation of NC cells from explanted neural tubes. These results suggest that GAL-1 plays a facilitative role in NC cell generation.