Satoshi Yoshinaga's research while affiliated with Keio University and other places

... We further explored the overlap of the various classes of eQTL among all enhancers in the EnhancerAtlas 2.0 (ref. 15) lung tissue enhancers, and the human lung epithelial cell line (Calu-3) enhancers, as well as cis-regulatory elements in the Human Cell Atlas 16 . Testing for the equality of proportions overlapping enhancer annotations between eQTLs and the null set, we found that multistate sc-eQTLs were more likely to which could go undetected in bulk RNA-seq of heterogeneous tissues. ...

... In the cerebral neocortex, a sensu lato non-cell-autonomous function of Reelin downstream signaling has been proposed. A previous study suggested that Dab1 À/À deep layer neurons, when present in high cell density below the subplate, became impermissible to the migration of Dab1 À/À superficial layer neurons, which otherwise had the potential to migrate past the subplate (Yoshinaga et al., 2022). Similarly, it is likely that Reelin acts on the interaction between the CLA and insular neurons. ...

... In clinical practice, cognitive-motor therapy, which emphasizes perceptual input and cognitive-driven movement, has been increasingly practiced clinically in improving walking ability in patients with cerebral infarction, especially in tasks requiring attention and processing speed, such as multitasking and gait adaptation tasks (Montero-Odasso et al., 2012). Some studies demonstrated the importance of cortical function for locomotion, as well as a greater emphasis on some methods to improve motor function by activating cognitive processes in the cortex (Fritz et al., 2015;Pothier et al., 2018;Hazra et al., 2022). In addition, cognitivemotor training, in which a cognitive task is performed alongside motor training, can more effectively strengthen the functional brain network connections between motor-cognitive brain areas and facilitate the activation of the cerebral cortex, thus promoting brain functional network remodeling and improving the patient's functional impairment (Caetano et al., 2017;Pang et al., 2018). ...

... Neither TNC nor NCAN was detected in the DKO mice, and the brain weights were not different compared to wild-type (WT) mice ( Figure 6-figure supplement 1). Since the migratory patterns of neurons differ between the lateral and medial cortices, we took advantage of Flash Tag technology, in which an intraventricular injection of fluorescent dyes allows for the pulse labeling of progenitors in contact with the ventricle across the brain (Govindan et al., 2018;Telley et al., 2016;Yoshinaga et al., 2021). Radial glial cells in the M-phase were labeled at E14.5, and their progeny was analyzed 2 days later at E16.5. ...

... These two sublayers harbor early-and late-born principal neurons, respectively, which migrate to the hippocampal or cortical plate in a birthtimedependent inside-out pattern [35,36]. Following the radial migration that occurs primarily during embryonic stage [37,38], principal neurons undergo a positioning step and subsequently become matured to develop synaptic connectivity [39,40]. The first 2weeks after birth are the critical period for neuron positioning and neuronal maturation in the cerebral cortex, during which the mouse hippocampal superficial and deep sublayers gradually condense into a compact lamina [41], while the neocortical principal cell layer expands markedly to form 5 loose laminae (Layer II-VI) [42][43][44][45]. ...

... However, the acquisition rate of conventional 2P-LSM is limited and millisecond transients such as APs can only be detected by drastically reducing the field of view (FOV) [36][37][38][39] . Although such approaches are valuable for imaging densely packed brain regions such as the hippocampus 40 , neurons in other brain regions are typically much sparser and hence require more specialised imaging approaches, based on spatial and/or temporal multiplexing to record neural activity across larger FOVs at kilohertz rates [41][42][43][44][45][46][47] . Since the neurons, and in particular, cell-body (somal) membranes generally occupy a small fraction of the total imaging volume, classical raster scan trajectories use the finite photon budget inefficiently 48 . ...

... Immunoelectron microscopy. Immunoelectron microscopy was performed as described previously (Shin et al., 2019). ICR mice were perfused with a fixative solution (4% PFA, 1% glutaraldehyde, and 0.1% picric acid in 0.1 M PB). ...

... Moreover, expression patterns of Pcdh genes have been examined in rodent brain regions involved in the neurocircuitry of MD 86 , with results indicating high expression levels in subregions of the hippocampus and basolateral amygdaloid complex 86,87 . The clustered PCDHA family also is strongly expressed in serotonergic neurons [88][89][90] and PcdhαC2 is necessary for axonal tiling and assembly of serotonergic circuitries 90 . Thus, a comprehensive understanding of the genetic architecture of the developing adolescent/young adult brain may be critical to identify etiological determinants of MD. ...

... To test this possibility, we performed time-lapse imaging and observed that some cells moved inward from the surface toward the deeper positions. This change in the migratory direction from outward to "inward" is a unique type of neuronal migration mode as opposed to conventional ones, such as "locomotion," "somal translocation," "terminal translocation," "multipolar migration," and "climbing mode" (Rakic, 1972;Nadarajah et al., 2001;Tabata and Nakajima, 2003;Noctor et al., 2004;Cooper, 2008;Tabata et al., 2009;Sekine et al., 2011Sekine et al., , 2012Yoshinaga et al., 2012;Kitazawa et al., 2014). Interestingly, although the CLA and insular cortex are close to each other in terms of location and birthdate, the migration profiles of CLA neurons were distinct from those of neurons in the insular cortex, which seemed to migrate only outward (Movie 1; Fig. 9). ...

... The advances obtained in the study of the human genome, and the alterations detected in patients with different neuropsychiatric pathologies have contributed to consolidating the generation of genetically modified animal models to uncover pathogenic mechanisms of behavioral alterations. However, the structural complexity of the nervous system and human behavior compared to other mammals (4)(5)(6)(7)(8) together with the polygenic nature of the genome alterations detected in psychiatric disorders (9), limited the progress of psychiatry based on preclinical studies using animal models. It must be taken into account that rodents, used more frequently in biomedical research, from an evolutionary point of view are more than 90 million years older in their origin compared to humans and have enormous structural and functional differences (10). ...