Taro Koike

The lateral line is a mechanosensory organ found in cyclostomes, teleosts, and amphibians. Hair cells within its neuromasts have kinocilia and stereocilia that sense water flow, and the lateral line nerve transduces this sensory input. Hair cells in the lateral line are analogous to those in the mammalian inner ear. Lateral line development and regeneration have been studied extensively in zebrafish. However, lateral line formation in other species remains poorly understood. The Iberian ribbed newt ( Pleurodeles waltl ) is a versatile model for regeneration with a short period of sexual maturation and aseasonal/prolific ovulation. Here, we investigated the features, regeneration processes, and additional neuromast formation in the posterior lateral line of Iberian ribbed newts using Brainbow reporters. The lateral line in the Iberian ribbed newts shares common features with other species. Laser ablation of hair cells or transection of the posterior lateral line nerve induced additional neuromast formation, to which epidermal cells contributed at least in part. We refer to it as “replicative neuromast regeneration” to allow distinction from several modes of neuromast formation in normal development. Based on these results, we propose that in response to injury, the posterior lateral line nerve induces epidermal cells to contribute to newly formed neuromasts in a replicative manner. Our results provide insights into lateral line morphogenesis.

Oncocytic adrenal neoplasms are rare adrenocortical tumors characterized by abundant eosinophilic cytoplasm due to massive mitochondrial accumulation. Their biological behavior is often difficult to predict, and various diagnostic systems—including the Lin–Weiss–Bisceglia system, the Helsinki score, and the reticulin algorithm—are used to assess their malignant potential. We report a case of an oncocytic adrenocortical carcinoma associated with Cushing's syndrome and hyperandrogenemia in a 34‐year‐old woman. Histologically, the tumor showed diffuse growth of eosinophilic cells with marked pleomorphism and focal capsular invasion. Immunohistochemistry confirmed adrenocortical origin and cortisol production, with a Ki‐67 labeling index of 25%. Ultrastructural examination revealed densely packed mitochondria with lamellar and tubulovesicular cristae, accompanied by numerous whorled smooth endoplasmic reticulum formations, suggesting active remodeling of the endoplasmic reticulum. Whole‐exome sequencing identified a pathogenic GNAS R201S mutation, together with copy number losses of ARID1A , CDKN2A , and ZNRF3 with widespread copy number alteration. Despite multiple adverse prognostic indicators, the patient has remained disease‐free for over 5 years following adrenalectomy and adjuvant low‐dose mitotane therapy. These findings suggest that GNAS activation may drive steroidogenesis while attenuating malignant progression, as demonstrated by integrated morphologic and genomic assessment in this case.

Many treatments for spinal cord injury (SCI) have been developed; however, none of these treatments enable complete functional repair. In this study, we utilized a model amphibian, Xenopus laevis , which has regeneration capacity of the spinal cord in the tadpole stages but loses it during metamorphosis, to identify differences in spinal cord properties between the regenerative and non‐regenerative stages. We compared the spatiotemporal expression patterns of transcription factors important for neural tube development as well as cell proliferation markers between tadpoles and metamorphosed young adults (froglets) in Xenopus as well as between Xenopus and mouse embryos. We found that Xenopus drastically changed properties in ependymal cells of the spinal cord during the transition from regenerative to non‐regenerative stages, and that similar change occurred in the mouse neural tube between 12.5 and 14.5 dpc, during which neurogenesis is known to cease. We then investigated neurogenic activity during Xenopus metamorphosis by labeling newly generated neurons and found that it was correlated with regeneration capacity. We also found that neurogenesis actively occurred after SCI at the regenerative stages but was scarcely reactivated at the non‐regenerative stages, suggesting that neurogenesis may play an important role in the process of spontaneous regeneration in Xenopus . We propose that supplying neurons as a treatment for SCI is a valid strategy based on principles of regeneration, which are naturally possessed by regenerative animals.

Rodents explore their environment by actively whisking and contacting objects with their whiskers. Each whisker follicle contains hundreds of mechanoreceptors, but how specific afferents distinguish between self-motion and touch remains unclear. Here, using artificial whisking in male rats, intra-axonal recordings, and morphological reconstruction, we identify a distinct mechanoreceptor subtype—club-like endings—that respond exclusively to touch and remain silent during whisking. In contrast, Merkel and lanceolate endings exhibit mixed selectivity. Club-like endings are arranged in a single-layer circular array near the center of mass of the whisker-follicle unit, embedded in a collagen-rich structure called the ringwulst. Using scanning electron microscopy, we show that these endings are tightly anchored to the glassy membrane and collagen fibers, forming a mechanically isolated zone. This configuration minimizes activation during whisking while preserving sensitivity to touch. We propose that these features evolved to enhance tactile precision in whisking species, as supported by the absence of such specializations in non-whisking animals such as cats.

Living organisms exhibit varying regenerative abilities depending on the species. Among them, urodele amphibians have been widely used in regeneration biology due to their remarkable regenerative capacity. Iberian ribbed newts, in particular, have been established as a prominent model for regeneration research, offering advantages such as a large number of eggs spawned, a short period of sexual maturation, and the development of genetic manipulation techniques. Cell tracing is an essential method for deciphering cellular processes during organ regeneration. The multicolor reporter Brainbow, which stochastically manifests multiple fluorescent proteins based on the Cre/lox recombination system, has been utilized for clonal analysis in regenerative animal models. In this study, we aimed to utilize this valuable multicolor reporter in Iberian ribbed newts, which are gaining increasing importance as a regenerative animal model. We generated transgenic Iberian ribbed newts carrying the Brainbow3.0 reporter cassette under the control of the CAG (cytomegalovirus early enhancer/chicken beta‐actin promoter/rabbit beta‐globin splice acceptor) promoter. Cre recombinase induction via electroporation led to recombinant reporter expression in the brain, spinal cord, and muscle. Recombinant reporter‐expressing cells could be traced in regenerating tail muscle, midbrain, and spinal cord. Additionally, we applied laser ablation to reporter‐positive epithelial cells of Brainbow3.0 newts, enabling clonal analyses at the cellular level. We expect that this long‐lasting multicolor reporter will prove versatile for a broad range of research fields.

Satellite glial cells (SGCs) cover the following two areas of a large‐diameter dorsal root ganglion (DRG) neuron: neuronal soma and initial region of the neuronal projection, namely Cajal's initial glomerulus (IG). The morphological and functional features of SGCs covering the neuronal soma have been studied extensively. However, those of SGCs surrounding the IG [periaxonal SGCs (aSGCs)] are poorly understood. In the present study, we aimed to investigate the histological characteristics of aSGCs in adult rats. The IG's length was approximately 120 μm, where approximately 10 aSGCs surrounded the IG. The SGC markers, including Kca2.3, Kir4.1, and FABP7, were obviously expressed in aSGCs located in the proximal and middle parts of the IG. Contrarily, the signal intensity of these cell markers decreased in aSGCs surrounding the distal part of the IG, and these cells expressed the promyelinating Schwann cell marker Oct‐6. Electron microscopy revealed aSGCs winding their thin processes around the IG. Additionally, the 5‐bromo‐2′‐deoxyuridine incorporation study demonstrated that these glial cells matured into myelinating Schwann cells. Oct‐6‐positive aSGCs were also found in the IG in the human DRG. Our results collectively imply that the IG is involved in the differentiation and maturation of Schwann cells, where aSGCs gradually change their ultrastructural characteristics and immunoreactivity to differentiate and mature into myelinating Schwann cells through the promyelinating stage, and that this differentiation and maturation system may be conserved among mammals.

The functional alteration of microglia arises in brains exposed to external stress during early development. Pathophysiological findings of neurodevelopmental disorders such as schizophrenia and autism spectrum disorder suggest cerebellar functional deficits. However, the link between stress-induced microglia reactivity and cerebellar dysfunction is missing. Here, we investigate the developmental immune environment in translational mouse models that combine two risk factors: maternal infection and repeated social defeat stress (2HIT). We find the synergy of inflammatory stress insults, leading to microglial increase specifically in the cerebellum of both sexes. Microglial turnover correlates with the Purkinje neuron loss in 2HIT mice. Highly multiplexed imaging-mass-cytometry identifies a cell transition to TREM2(+) stress-associated microglia in the cerebellum. Single-cell-proteomic clustering reveals IL-6- and TGFβ-signaling association with microglial cell transitions. Reduced excitability of remaining Purkinje cells, cerebellum-involved brain-wide functional dysconnectivity, and behavioral abnormalities indicate cerebellar cognitive dysfunctions in 2HIT animals, which are ameliorated by both systemic and cerebellum-specific microglia replacement.

Satellite glial cells in the dorsal root ganglion are integral to the biology of sensory neurons. This review explores their unique fine structures, as well as their roles in pain signaling and neuronal differentiation. Satellite glial cells exhibit remarkable plasticity, including stem cell-like properties and the ability to influence neuronal morphology and function. Less-studied glial types, such as axonic satellite glial cells and newly identified glial populations, also offer insights into glial cell diversity and specialization. By focusing on the cellular and molecular mechanisms underlying satellite glial cell function, this review contributes to enhancing the foundational understanding of sensory system organization and glial biology.

In the M‐phase, the nuclear membrane is broken down, nucleosomes are condensed as mitotic chromosomes, and transcription factors are generally known to be dislocated from their recognition sequences and dispersed to the cytoplasm. However, some transcription factors have recently been reported to remain on mitotic chromosomes and facilitate the rapid re‐activation of the target genes in early G1‐phase. Paired‐like homeobox 2B (PHOX2B) is a transcription factor exhibiting chromosomal localization during M‐phase. PHOX2B mutations are associated with congenital central hypoventilation syndrome, Hirschsprung disease, and neuroblastoma. In this study, we investigated PHOX2B chromosomal localization during M‐phase through immunostaining and fluorescence recovery after photobleaching analysis to determine whether the chromosomal localization of disease‐associated PHOX2B mutants is altered during M‐phase. Missense mutations in the homeodomain and the frameshift mutation in the C‐terminal domain disrupted the chromosomal localization of PHOX2B in M‐phase, leading to its dispersion in the cell. Furthermore, a PHOX2B mutant with polyalanine expansion showed a line‐shaped localization to the restricted region of mitotic chromosomes. Our findings suggest an association between the disease‐associated mutations and defective chromosomal localization of transcription factors during M‐phase. Further investigations of PHOX2B chromosomal localization during M‐phase could reveal pathogenic mechanisms of such diseases.