Computational cell model based on autonomous cell movement regulated by cell-cell signalling successfully recapitulates the "inside and outside" pattern of cell sorting

<p>Abstract</p> <p>Background</p> <p>Development of multicellular organisms proceeds from a single fertilized egg as the combined effect of countless numbers of cellular interactions among highly dynamic cells. Since at least a reminiscent pattern of morphogenesis can be recapitulated in a reproducible manner in reaggregation cultures of dissociated embryonic cells, which is known as cell sorting, the cells themselves must possess some autonomous cell behaviors that assure specific and reproducible self-organization. Understanding of this self-organized dynamics of heterogeneous cell population seems to require some novel approaches so that the approaches bridge a gap between molecular events and morphogenesis in developmental and cell biology. A conceptual cell model in a computer may answer that purpose. We constructed a dynamical cell model based on autonomous cell behaviors, including cell shape, growth, division, adhesion, transformation, and motility as well as cell-cell signaling. The model gives some insights about what cellular behaviors make an appropriate global pattern of the cell population.</p> <p>Results</p> <p>We applied the model to "inside and outside" pattern of cell-sorting, in which two different embryonic cell types within a randomly mixed aggregate are sorted so that one cell type tends to gather in the central region of the aggregate and the other cell type surrounds the first cell type. Our model can modify the above cell behaviors by varying parameters related to them. We explored various parameter sets with which the "inside and outside" pattern could be achieved. The simulation results suggested that direction of cell movement responding to its neighborhood and the cell's mobility are important for this specific rearrangement.</p> <p>Conclusion</p> <p>We constructed an <it>in silico </it>cell model that mimics autonomous cell behaviors and applied it to cell sorting, which is a simple and appropriate phenomenon exhibiting self-organization of cell population. The model could predict directional cell movement and its mobility are important in the "inside and outside" pattern of cell sorting. Those behaviors are altered by signal molecules and consequently affect the global pattern of the cell sorting. Our model is also applicable to other developmental processes beyond cell sorting.</p

Amphiphilic peptide-tagged N-cadherin forms radial glial-like fibers that enhance neuronal migration in injured brain and promote sensorimotor recovery

The mammalian brain has very limited ability to regenerate lost neurons and recover function after injury. Promoting the migration of young neurons (neuroblasts) derived from endogenous neural stem cells using biomaterials is a new and promising approach to aid recovery of the brain after injury. However, the delivery of sufficient neuroblasts to distant injured sites is a major challenge because of the limited number of scaffold cells that are available to guide neuroblast migration. To address this issue, we have developed an amphiphilic peptide [(RADA)3-(RADG)] (mRADA)-tagged N-cadherin extracellular domain (Ncad-mRADA), which can remain in mRADA hydrogels and be injected into deep brain tissue to facilitate neuroblast migration. Migrating neuroblasts directly contacted the fiber-like Ncad-mRADA hydrogel and efficiently migrated toward an injured site in the striatum, a deep brain area. Furthermore, application of Ncad-mRADA to neonatal cortical brain injury efficiently promoted neuronal regeneration and functional recovery. These results demonstrate that self- assembling Ncad-mRADA peptides mimic both the function and structure of endogenous scaffold cells and provide a novel strategy for regenerative therapy

Biomaterial-engineering and neurobiological approaches for regenerating the injured cerebral cortex

The cerebral cortex is responsible for higher functions of the central nervous system (CNS), such as movement, sensation, and cognition. When the cerebral cortex is severely injured, these functions are irreversibly impaired. Although recent neurobiological studies reveal that the cortex has the potential for regeneration, therapies for functional recovery face some technological obstacles. Biomaterials have been used to evoke regenerative potential and promote regeneration in several tissues, including the CNS. This review presents a brief overview of new therapeutic strategies for cortical regeneration from the perspectives of neurobiology and biomaterial engineering, and discusses a promising technology for evoking the regenerative potential of the cerebral cortex

β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain

Teppei Fujioka, Naoko Kaneko, Itsuki Ajioka, Kanako Nakaguchi, Taichi Omata, Honoka Ohba, Reinhard Fässler, José Manuel García-Verdugo, Kiyotoshi Sekiguchi, Noriyuki Matsukawa, and Kazunobu Sawamoto, "β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain", EBioMedicine, 16, 195-203, Elsevier, 201

Detailed Expression Pattern of Aldolase C (Aldoc) in the Cerebellum, Retina and Other Areas of the CNS Studied in Aldoc-Venus Knock-In Mice

Aldolase C (Aldoc, also known as ‘‘zebrin II’’), a brain type isozyme of a glycolysis enzyme, is expressed heterogeneously insubpopulations of cerebellar Purkinje cells (PCs) that are arranged longitudinally in a complex striped pattern in thecerebellar cortex, a pattern which is closely related to the topography of input and output axonal projections. Here, wegenerated knock-in Aldoc-Venus mice in which Aldoc expression is visualized by expression of a fluorescent protein, Venus.Since there was no obvious phenotypes in general brain morphology and in the striped pattern of the cerebellum inmutants, we made detailed observation of Aldoc expression pattern in the nervous system by using Venus expression inAldoc-Venus heterozygotes. High levels of Venus expression were observed in cerebellar PCs, cartwheel cells in the dorsalcochlear nucleus, sensory epithelium of the inner ear and in all major types of retinal cells, while moderate levels of Venusexpression were observed in astrocytes and satellite cells in the dorsal root ganglion. The striped arrangement of PCs thatexpress Venus to different degrees was carefully traced with serial section alignment analysis and mapped on the unfoldedscheme of the entire cerebellar cortex to re-identify all individual Aldoc stripes. A longitudinally striped boundary of Aldocexpression was first identified in the mouse flocculus, and was correlated with the climbing fiber projection pattern andexpression of another compartmental marker molecule, heat shock protein 25 (HSP25). As in the rat, the cerebellar nucleiwere divided into the rostrodorsal negative and the caudoventral positive portions by distinct projections of Aldoc-positiveand negative PC axons in the mouse. Identification of the cerebellar Aldoc stripes in this study, as indicated in samplecoronal and horizontal sections as well as in sample surface photos of whole-mount preparations, can be referred to infuture experiment

Detailed expression pattern of aldolase C (Aldoc) in the cerebellum, retina and other areas of the CNS studied in Aldoc-Venus knock-in mice.

Aldolase C (Aldoc, also known as "zebrin II"), a brain type isozyme of a glycolysis enzyme, is expressed heterogeneously in subpopulations of cerebellar Purkinje cells (PCs) that are arranged longitudinally in a complex striped pattern in the cerebellar cortex, a pattern which is closely related to the topography of input and output axonal projections. Here, we generated knock-in Aldoc-Venus mice in which Aldoc expression is visualized by expression of a fluorescent protein, Venus. Since there was no obvious phenotypes in general brain morphology and in the striped pattern of the cerebellum in mutants, we made detailed observation of Aldoc expression pattern in the nervous system by using Venus expression in Aldoc-Venus heterozygotes. High levels of Venus expression were observed in cerebellar PCs, cartwheel cells in the dorsal cochlear nucleus, sensory epithelium of the inner ear and in all major types of retinal cells, while moderate levels of Venus expression were observed in astrocytes and satellite cells in the dorsal root ganglion. The striped arrangement of PCs that express Venus to different degrees was carefully traced with serial section alignment analysis and mapped on the unfolded scheme of the entire cerebellar cortex to re-identify all individual Aldoc stripes. A longitudinally striped boundary of Aldoc expression was first identified in the mouse flocculus, and was correlated with the climbing fiber projection pattern and expression of another compartmental marker molecule, heat shock protein 25 (HSP25). As in the rat, the cerebellar nuclei were divided into the rostrodorsal negative and the caudoventral positive portions by distinct projections of Aldoc-positive and negative PC axons in the mouse. Identification of the cerebellar Aldoc stripes in this study, as indicated in sample coronal and horizontal sections as well as in sample surface photos of whole-mount preparations, can be referred to in future experiments