Biology subjects

Ema, M.

Publications and source records attributed to Ema, M..

7 recordsLinked to original sources

bioRxiv2024

Neuronal migration depends on blood flow in the adult brain

In animal tissues, several cell types migrate along blood vessels, raising the possibility that blood flow influences cell migration. Here, we show that blood flow promotes the migration of new olfactory-bulb neurons in the adult brain. Neuronal migration is facilitated by blood flow, leading to accumulation of new neurons near blood vessels with abundant blood flow. Blood flow inhibition attenuates blood vessel-guided neuronal migration, suggesting that blood contains factors beneficial to neuronal migration. We found that ghrelin, which is increased in blood by hunger, directly influences neuronal migration. Ghrelin signaling promotes somal translocation by activating actin cytoskeleton contraction at the rear of the cell soma. New neurons mature in the olfactory bulb and contribute to the olfactory function for sensing odorants from food. Finally, we show that neuronal migration is increased by calorie restriction, and that ghrelin signaling is involved in the process. This study suggests that blood flow promotes neuronal migration through blood-derived ghrelin signaling in the adult brain, which could be one of the mechanisms that improves the olfactory function for food-seeking behavior during starvation.

neuroscience↗

bioRxiv2023

Highly efficient transgenic mouse production using piggyBac and its application to rapid phenotyping at the founder generation

Pronuclear microinjection is the most popular method for producing transgenic (Tg) animals. Because the production efficiency is typically less than 20%, phenotypic characterization of Tg animals is generally performed on the next generation (F1) onwards. However, apart from in rodents, in many animal species with long generation times, it is desirable to perform phenotyping in the founder (F0) generation. In this study, we attempted to optimize a method of Tg mouse production to achieve higher Tg production efficiency using piggyBac transposon systems and established optimal conditions under which almost all individuals in the F0 generation were Tg. We also succeeded in generating bacterial artificial chromosome Tg mice with efficiency of approximately 70%. By combining this method with genome editing technology, we established a new strategy to perform phenotyping of mice with tissue-specific knockout using the F0 generation. Taking the obtained findings together, by using this method, experimental research using Tg animals can be carried out more efficiently.

bioengineering↗

bioRxiv2022

KLF5-regulated extracellular matrix remodeling secures biliary epithelial tissue integrity against cholestatic liver injury

Abstract / Introductory paragraphTubular epithelial tissues in the body play fundamental roles as infrastructure constituting conduits to transport various types of biological fluids, for which contiguous and integrated epithelial tissue structures should be maintained continuously and even under stressed conditions. Compared to tissue morphological processes that take place during ontogeny, the mechanisms whereby tubular epithelial tissues maintain their structural integrity in adulthood remains largely unclear. Here, we show that the transcription factor Klf5 is crucial for maintaining the biliary epithelial integrity in tissue remodeling processes induced under cholestatic injury conditions in the adult liver. Loss of Klf5 in the biliary epithelia led to tissue collapse in vivo in injured mouse livers, as well as in vitro in bile ductular organoids in a tissue-autonomous manner and independent of cell proliferation. Klf5 regulated cell junction organization and cell adhesion, along with extracellular matrix remodeling around the expanding biliary epithelia through deposition of Lamb3-containing laminin complexes. Targeting the Lamb3 expression in biliary epithelia in mice recapitulated the tissue collapse phenotype. Together, our results highlight a novel mechanism whereby the epithelial tissue maintains its integrity while undergoing unstable structural transformation.

developmental biology↗

bioRxiv2020

Chromosomal-scale De novo Genome Assemblies of Cynomolgus Macaque and Common Marmoset

Cynomolgus macaque (Macaca fascicularis) and common marmoset (Callithrix jacchus) have been widely used in human biomedical research. Their genomes were sequenced and assembled initially using short-read sequences, with the advent of massively parallel sequencing. However, the resulting contig sequences tended to remain fragmentary, and long-standing primate genome assemblies used the human genome as a reference for ordering and orienting the assembled fragments into chromosomes. Here we performed de novo genome assembly of these two species without any human genome-based bias observed in the genome assemblies released earlier. Firstly we assembled PacBio long reads, and the resultant contigs were scaffolded with Hi-C data. The scaffolded sequences obtained were further refined based on assembly results of alternate de novo assemblies and Hi-C contact maps by resolving identified inconsistencies. The final assemblies achieved N50 lengths of 149 Mb and 137 Mb for cynomolgus macaque and common marmoset, respectively, and the numbers of scaffolds longer than 10Mb are equal to their chromosome numbers. The high fidelity of our assembly is ascertained by concordance to the BAC-end read pairs observed for common marmoset, as well as a high resemblance of their karyotypic organization. Our assembly of cynomolgus macaque outperformed all the available assemblies of this species in terms of contiguity. The chromosome-scale genome assemblies produced in this study are valuable resources for non-human primate models and provide an important baseline in human biomedical research.

genomics↗

bioRxiv2020

EXOC1 regulates cell morphology of spermatogonia and spermatocytes in mice

Spermatogenesis requires high regulation of germ cell morphology. The spermatogonia regulates its differentiation state by its own migration. The male germ cells differentiate and mature with the formation of syncytia, failure of forming the appropriate syncytia results in the arrest of spermatogenesis at the spermatocyte stage. However, the detailed molecular mechanisms of male germ cell morphological regulation are unknown. Here, we found that EXOC1 is important for the pseudopod formation of spermatogonia and spermatocyte syncytia in mice. We found that while EXOC1 contributes to the inactivation of Rac1 in the pseudopod formation of spermatogonia, in spermatocyte syncytium formation, EXOC1 and SNAP23 cooperate with STX2. Our results showed that EXOC1 functions in concert with various cell morphology regulators in spermatogenesis. Since EXOC1 is known to bind to several cell morphogenesis factors, this study is expected to be the starting point for the discovery of many morphological regulators of male germ cells.

developmental biology↗

bioRxiv2019

Organogenesis and Distribution of the Ocular Lymphatic Vessels in the Anterior Eye: Implication to Glaucoma Surgery Site Selection

Glaucoma surgeries, such as trabeculectomy, are performed to lower the intraocular pressure to reduce the risk of vision loss. The surgeries create a new passage in the eye that reroutes the aqueous humor outflow to the subconjunctival space, where the fluid is presumably absorbed by the conjunctival lymphatics. However, the current knowledge of these ocular surface lymphatics remains limited. Here, we characterized the biology and function of the ocular lymphatics using transgenic lymphatic reporter mice and rats. We found that the limbal and conjunctival lymphatic networks are progressively formed by a primary lymphatic vessel that grows out from the nasal-side medial canthus region at the time of birth. This primary lymphatic vessel immediately branches out and invades the limbus and conjunctiva, and then simultaneously encircles the cornea in a bidirectional manner. As a result, the distribution of the ocular lymphatic is significantly polarized toward the nasal side, and the limbal lymphatics are directly connected to the conjunctival lymphatics. New lymphatic spouts are mainly produced from the nasal-side limbal lymphatics, posing the nasal side of the eye more responsive to fluid drainage and inflammatory stimuli. Consistently, when a fluorescent tracer was injected, fluid clearance was much more efficient in the nasal side than the temporal side of the eyes. In comparison, blood vessels are evenly distributed on the front surface of the eyes. We found that these distinct vascular distribution patterns were also conserved in human eyes. Together, our study demonstrated that the ocular surface lymphatics are more densely present in the nasal side and uncovered the potential clinical benefits in selecting the nasal side as a surgical site for glaucoma surgeries to improve the fluid drainage.

developmental biology↗

bioRxiv2019

Cables2 Is a novel Smad2-regulatory factor essential for early embryonic development in mice

CDK5 and Abl enzyme substrate 2 (Cables2), a member of the Cables family that has a C-terminal cyclin box-like domain, is widely expressed in adult mouse tissues. However, the physiological role of Cables2 in vivo is unknown. We show here that Cables2-deficiency causes post-gastrulation embryonic lethality in mice. The mutant embryos progress to gastrulation, but then arrest, and fail to grow. Analysis of gene expression patterns reveals that formation of the anterior visceral endoderm and the primitive streak is impaired in Cables2-deficient embryos. Tetraploid complementation analyses support the critical requirement of Cables2 in both the epiblast and visceral endoderm for progression of embryogenesis. In addition, we show that Cables2 physically interacts with a key mediator of the canonical Nodal pathway, Smad2, and augments its transcriptional activity. These findings provide novel insights into the essential role of Cables2 in the early embryonic development in mice.

developmental biology↗