Biology subjects

Furukawa, F.

Publications and source records attributed to Furukawa, F..

5 recordsLinked to original sources

bioRxiv2026

Evolutionary insights into glucose production in vertebrate development: new findings from Arctic lamprey (Lethenteron camtschaticum)

Glucose has important roles in the development of the hematopoietic stem cells and the brain in vertebrate embryos; however, in most oviparous animals, the amount of glucose in the yolk is scarce. In zebrafish, gluconeogenesis takes place in the yolk syncytial layer (YSL), an extraembryonic tissue that surrounds the yolk. Gluconeogenic activity have also been observed in extraembryonic YSL-like tissue or endoderm-derived tissues in cloudy catshark, sterlet, and western clawed frog during development. However, it remains unclear when such ability was acquired or how it changed over the evolution of vertebrates. In this study, we used the Arctic lamprey, a cyclostome sister group of jawed vertebrates, to compare changes in metabolite levels and gluconeogenic gene expression patterns during development. Also, gluconeogenic activity was assessed using 13C-labeled substrates. Our metabolite analysis revealed that glucose levels increased during development and that glycerol was actively metabolized to produce glucose. In addition, many gluconeogenic genes were expressed in the muscle, notochord, and epithelium, making a striking contrast to previous observations in the above-mentioned vertebrates. Genomic DNA sequence motif analysis using HOMER and MEME identified common transcription factors binding motifs in the upstream regions of g6pc1/2 and fbp1 across vertebrate lineages. Among them, interestingly, the binding motif for HNF4A was not detected in g6pc1/2 and fbp1 genes of cyclostomes, suggesting distinct transcriptional regulation of gluconeogenesis in cyclostomes. These results indicate that gluconeogenesis is an essential process during development across vertebrate lineages, including cyclostomes, although the tissues and regulatory mechanisms for this function vary among lineages.

developmental biology↗

bioRxiv2026

Gluconeogenesis and glycogen metabolism in the epidermis and endoderm of Xenopus tropicalis embryos and larvae.

In many oviparous animals, egg yolk is the sole source of nutrition until feeding begins, and carbohydrates are present in only small amounts in the yolk. Glucose plays an important role in the developmental processes of various animals. In addition, gluconeogenesis has been reported to occur in the yolk syncytial layer (YSL) of cartilaginous fish and teleosts. In contrast, the role of gluconeogenesis in tetrapods remains unclear. In this study, we used Xenopus tropicalis, an anuran amphibian, which lacks YSL, and therefore provide an opportunity to examine the evolutionary conservation of gluconeogenic mechanisms among vertebrates. In X. tropicalis, liquid chromatography/mass spectrometry revealed that glucose levels increased before liver formation. Subsequent tracer experiments using 13C-labeled metabolic substrates detected gluconeogenesis activity from glycerol and lactate. Expression analyses showed that gluconeogenic genes are expressed in the epidermis and endoderm. Consistently, generation 0 (G0) knockout of fbp1, a key gluconeogenic gene, resulted in a significant reduction in glucose levels, affecting brain development. These findings first demonstrate that gluconeogenesis supports development of X. tropicalis. To the best of our knowledge, gluconeogenesis in developing epidermis has not been reported, highlighting previously unrecognized diversity in tissue-specific metabolism during vertebrate development. Comparative analyses across species will provide further insights into the evolution and functional significance of embryonic gluconeogenesis and nutrient metabolism.

developmental biology↗

bioRxiv2024

Gluconeogenesis in the YSL-like tissue of cloudy catshark (Scyliorhinus torazame).

Glucose has important roles in the development of hematopoietic stem cells and brain of zebrafish, the vertebrate animal model; however, in most oviparous animals, the amount of maternally provided glucose in the yolk is scarce. For these reasons, developing animals need some ways to supplement glucose. Recently, it was found that developing zebrafish, a teleost fish, undergo gluconeogenesis in the yolk syncytial layer (YSL), an extraembryonic tissue that surrounds the yolk, utilizing yolk nutrients as substrates. However, teleost YSL is evolutionarily unique, and it is not clear how other vertebrates supplement glucose. In this study, we used cloudy catshark, an elasmobranch species which possesses a YSL-like tissue during development, and sought for possible gluconeogenic activities in this tissue. In the catshark yolk sac, an increase in glucose level was found, and our isotope tracking by 13C-labeled substrate combined with LC/MS analysis detected gluconeogenic activities with glycerol most preferred substrate. In addition, expression analysis for gluconeogenic genes showed that many of these were expressed at the YSL-like tissue, suggesting that cloudy catshark engages in gluconeogenesis in this tissue. The gluconeogenesis in teleost YSL and a similar tissue in elasmobranch species implies conservation of the mechanisms of yolk metabolism between these two lineages. Future studies on other vertebrate taxa will be helpful to understand the evolutionary changes in the modes of yolk metabolism that vertebrates have experienced.

physiology↗

bioRxiv2023

Maternal high-fat diet affects the contents of eggs and causes abnormal development in the medaka fish

Maternal nutritional status can affect development and metabolic phenotypes of their progeny in animals. The effects of maternal diet are thought to be mediated mainly by changes inside oocytes such as organelles, maternal RNAs, and metabolites. However, to what extent each factor contributes to offspring phenotypes remains uncertain, especially in viviparous mammalian systems, where factors other than oocytes, such as placenta and milk, need to be considered. Here, using the medaka fish as an oviparous vertebrate model, we examined whether maternal high-fat diet (mHFD) feeding affects offspring development, and what kind of changes occur in the contents of mature eggs. We found that mHFD caused the high frequency of embryonic deformities of offspring, accompanied by downregulation of transcription- and translation-related genes and zygotic transcripts at the blastula stage. Transcriptomic and metabolomic analyses of mature eggs suggested decreased catabolism of amino acids and glycogen, moderate upregulation of endoplasmic reticulum stress-related genes, and elevated lipid levels in mHFD eggs. Furthermore, HFD females showed upregulation of follicle-stimulating hormone, a higher incidence of oocyte atresia and downregulation of egg protein genes in the liver. These data suggested that attenuated amino acid catabolism triggered by decreased yolk protein load/processing, as well as elevated lipid levels inside eggs, are the prime candidates that account for the higher incidence of embryonic deformities in mHFD offspring. Our study presents a comprehensive data on the changes inside eggs in mHFD model of non-mammalian vertebrates, and provides insights into the mechanisms of parental nutritional effects on their offspring.

physiology↗

bioRxiv2019

Pivotal involvement of the CX3CL1-CX3CR1 axis for the recruitment of M2-TAMs in skin carcinogenesis

We previously revealed the crucial roles of CX3CL1-CX3CR1 axis in skin wound healing. Although repeated wounds frequently develop into skin cancer, the roles of CX3CL1 in skin carcinogenesis remain elusive. Here, we proved that CX3CL1 protein expression and CX3CR1+ macrophages were observed in human skin cancer tissues. Similarly, we observed the enhancement of CX3CL1 expression and the abundant accumulation of CX3CR1+ tumor-associated macrophages (TAMs) with M2 phenotypes in the skin carcinogenesis process induced by the combined treatment with 7,12-dimethylbenz-(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). In this mouse skin carcinogenesis process, CX3CR1+ TAMs exhibited M2 phenotypes with the expression of Wnt3a and angiogenic molecules including vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9. Compared to wild-type mice, CX3CR1-deficient mice showed fewer numbers of skin tumors with a lower incidence. Concomitantly, M2-macrophage numbers and neovascularization reduced with the depressed expression of angiogenic factors and Wnt3a. Thus, the CX3CL1-CX3CR1 axis can crucially contribute to skin carcinogenesis by regulating the accumulation and functions of TAMs. Thus, this axis can be a good target for preventing and/or treating skin cancers.

cancer biology↗