About

Hiroshi Nakato, PhD, is a professor in the Department of Genetics, Cell Biology and Development at the University of Minnesota Medical School. The page provides his professional title and affiliation but does not include specific details about his research focus, background, or key contributions.

Research topics

• Cell biology
• Biology
• Biochemistry
• Genetics

Selected publications

• Data for Chondroitin sulfate regulates proliferation of Drosophila intestinal stem cells

  Data Repository for the University of Minnesota · 2026-01-01

  datasetOpen accessSenior author

  This dataset provides raw confocal microscopy images and quantitative data underlying the figures presented in our published study on the Drosophila midgut. The dataset includes original image files and unprocessed numerical data used for graph generation and statistical analyses. These data were collected to investigate the role of chondroitin sulfate and basement membrane remodeling in the regulation of intestinal stem cell activity during homeostasis and regeneration. This dataset captures imaging-based measurements of stem cell proliferation and tissue responses under defined genetic and experimental conditions. By providing access to the raw data, this dataset supports transparency, reproducibility, and independent reanalysis of the results reported in the associated publication, and it serves as a resource for further studies on stem cell regulation and tissue regeneration.

  PublisherDOI

• Chondroitin sulfate regulates proliferation of Drosophila intestinal stem cells

  PLoS Genetics · 2025-05-09 · 1 citations

  articleOpen accessSenior author

  The basement membrane (BM) plays critical roles in stem cell maintenance and activity control. Here we show that chondroitin sulfate (CS), a major component of the Drosophila midgut BM, is required for proper control of intestinal stem cells (ISCs). Loss of Chsy, a critical CS biosynthetic gene, resulted in elevated levels of ISC proliferation during homeostasis, leading to midgut hyperplasia. Regeneration assays demonstrated that Chsy mutant ISCs failed to properly downregulate mitotic activity at the end of regeneration. We also found that CS is essential for the barrier integrity to prevent leakage of the midgut epithelium. CS is known to be polymerized by the action of the complex of Chsy and another critical protein, Chondroitin polymerizing factor (Chpf). We found that Chpf mutants show increased ISC division during midgut homeostasis and regeneration, similar to Chsy mutants. As Chpf is induced by a tissue damage during regeneration, our data suggest that Chpf functions with Chsy to facilitate CS remodeling and stimulate tissue repair. We propose that the completion of the repair of CS-containing BM acts as a prerequisite to properly terminate the regeneration process.

  PublisherDOI

• In vivo analysis of Drosophila chondroitin sulfate biosynthetic genes

  Journal of Biological Chemistry · 2025-10-07

  articleOpen accessSenior author

  Chondroitin sulfate (CS) is an evolutionarily conserved class of glycosaminoglycans and is found in most animal species. Previous studies of CS-deficient Drosophila models, Chondroitin sulfate synthase (Chsy), and Chondroitin polymerizing factor (Chpf) mutants demonstrated the importance of CS in the structural integrity of the basement membrane and organ shape maintenance. However, biosynthetic mechanisms of Drosophila CS remain to be elucidated. To investigate the CS biosynthesis in Drosophila, we generated mutants for two additional biosynthetic enzyme genes, CS N-acetylgalactosaminyltransferase (Csgalnact) and CS 4-O sulfotransferase (C4st), using CRISPR-Cas9 mutagenesis. Csgalnact-null mutants show moderate changes in CS biosynthesis, including reduced CS in the larval brain and altered CS chain length. We found that this gene is dispensable for normal viability and morphogenesis. On the other hand, C4st mutants show more severe defects, including a high level of lethality and a folded wing phenotype. The C4st mutation not only eliminates CS sulfation but increases production of unsulfated chondroitin, suggesting the existence of a compensatory feedback mechanism. Both Csgalnact and C4st mutants show impaired adult negative geotaxis behavior, consistent with the role of CS proteoglycan in the neuromuscular systems. Our study revealed unique and poorly understood features of invertebrate CS biosynthesis and provides novel in vivo toolsets to investigate CSPG functions in development.

  PublisherDOI

• Chondroitin sulfate in invertebrate development

  Proteoglycan Research · 2024-10-01 · 1 citations

  articleOpen accessSenior authorCorresponding

  Abstract Chondroitin sulfate (CS) is one of the most evolutionarily conserved glycosaminoglycans (GAGs). Although CS's function in skeletal development is well established in vertebrates, CS exists in more primitive animal species with no cartilage or bone, such as C. elegans and Drosophila , indicating that the original role of CS was not in the skeletal system. In this review, we focus on the roles of CS and the mechanisms of action during development of two genetically trackable model organisms, C. elegans and Drosophila .

  PublisherOA PDFDOI

• In vivo activities of heparan sulfate differentially modified by NDSTs during development

  Proteoglycan Research · 2024-01-01 · 1 citations

  articleOpen accessSenior authorCorresponding

  Abstract Heparan sulfate proteoglycans (HSPGs) serve as co‐receptors for growth factor signaling during development. It is well known that the level and patterns of sulfate groups of heparan sulfate (HS) chains, or HS fine structures, have a major impact on HSPG function. On the other hand, the physiological significance of other structural features of HS, including NS/NA domain organization, remains to be elucidated. A blueprint of the HS domain structures is mainly controlled by HS N ‐deacetylase/ N ‐sulfotransferases (NDSTs). To analyze in vivo activities of differentially modified HS, we established two knock‐in (KI) Drosophila strains with the insertion of mouse Ndst1 ( mNdst1 ) or Ndst2 ( mNdst2 ) in the locus of sulfateless ( sfl ), the only Drosophila NDST. In these KI lines, mNDSTs are expressed from the sfl locus, in the level and patterns identical to the endogenous sfl gene. Thus, phenotypes of Ndst1 KI and Ndst2 KI animals reflect the ability of HS structures made by these enzymes to rescue sfl mutation. Remarkably, we found that mNdst1 completely rescued the loss of sfl . mNdst2 showed a limited rescue ability, despite a higher level of HS sulfation compared to HS in mNdst1 KI. Our study suggests that independent of sulfation levels, additional HS structural features controlled by NDSTs play key roles during tissue patterning.

  PublisherOA PDFDOI

• Differential heparan sulfate dependency of the Drosophila glypicans

  Journal of Biological Chemistry · 2023 · 5 citations

  Senior authorCorresponding
  • Biology
  • Genetics
  • Cell biology

  mutants do not show most of the dlp null mutant phenotypes, suggesting that HS chains are dispensable for these dlp functions. As an exception, HS is essentially required for Dlp's activity at the neuromuscular junction. Thus, Drosophila glypicans show strikingly different levels of HS dependency. The ΔGAG mutant alleles of the glypicans serve as new molecular genetic toolsets highly useful to address important biological questions, such as molecular mechanisms of morphogen gradient formation.

  PublisherOA PDFDOI

• Chondroitin sulfate is required for follicle epithelial integrity and organ shape maintenance in <i>Drosophila</i>

  Development · 2023-09-01 · 6 citations

  articleOpen accessSenior author

  Heparan sulfate (HS) and chondroitin sulfate (CS) are evolutionarily conserved glycosaminoglycans that are found in most animal species, including the genetically tractable model organism Drosophila. In contrast to extensive in vivo studies elucidating co-receptor functions of Drosophila HS proteoglycans (PGs), only a limited number of studies have been conducted for those of CSPGs. To investigate the global function of CS in development, we generated mutants for Chondroitin sulfate synthase (Chsy), which encodes the Drosophila homolog of mammalian chondroitin synthase 1, a crucial CS biosynthetic enzyme. Our characterizations of the Chsy mutants indicated that a fraction survive to adult stage, which allowed us to analyze the morphology of the adult organs. In the ovary, Chsy mutants exhibited altered stiffness of the basement membrane and muscle dysfunction, leading to a gradual degradation of the gross organ structure as mutant animals aged. Our observations show that normal CS function is required for the maintenance of the structural integrity of the ECM and gross organ architecture.

  PublisherDOI

• Regulation of morphogen pathways by a <i>Drosophila</i> chondroitin sulfate proteoglycan Windpipe

  Journal of Cell Science · 2023-03-10 · 5 citations

  articleOpen accessSenior author

  Morphogens provide quantitative and robust signaling systems to achieve stereotypic patterning and morphogenesis. Heparan sulfate (HS) proteoglycans (HSPGs) are key components of such regulatory feedback networks. In Drosophila, HSPGs serve as co-receptors for a number of morphogens, including Hedgehog (Hh), Wingless (Wg), Decapentaplegic (Dpp) and Unpaired (Upd, or Upd1). Recently, Windpipe (Wdp), a chondroitin sulfate (CS) proteoglycan (CSPG), was found to negatively regulate Upd and Hh signaling. However, the roles of Wdp, and CSPGs in general, in morphogen signaling networks are poorly understood. We found that Wdp is a major CSPG with 4-O-sulfated CS in Drosophila. Overexpression of wdp modulates Dpp and Wg signaling, showing that it is a general regulator of HS-dependent pathways. Although wdp mutant phenotypes are mild in the presence of morphogen signaling buffering systems, this mutant in the absence of Sulf1 or Dally, molecular hubs of the feedback networks, produces high levels of synthetic lethality and various severe morphological phenotypes. Our study indicates a close functional relationship between HS and CS, and identifies the CSPG Wdp as a novel component in morphogen feedback pathways.

  PublisherOA PDFDOI

• Heparan Sulfate Proteoglycans in the Stem Cell Niche: Lessons from Drosophila

  Biology of extracellular matrix · 2021-01-01 · 3 citations

  book-chapterSenior author
  PublisherDOI

• Endogenous epitope tagging of a JAK/STAT ligand Unpaired1 in Drosophila

  PubMed · 2021-04-16 · 2 citations

  articleOpen accessSenior author

  expression patterns revealed by previous studies. This transgenic fly strain will be useful in studying the expression, localization, and association partners of Upd1, and thus will contribute to understanding how activation of the JAK/STAT pathway is regulated.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01HD042769

  NIH · $2.6M · 2015

• NIH Grant R01GM067208

  NIH · $1.2M · 2010

• Genetic Study of Heparan Sulfate Function in Development

  NIH · $1.2M · 2002–2020

• Heparan sulfate proteoglycans in signaling and development

  NIH · $2.2M · 2019–2030

Frequent coauthors

• Keisuke Kamimura

  Tokyo Metropolitan Institute of Medical Science

  18 shared

• Masahiko Takemura

  University of Minnesota

  17 shared

• Susumu Izumi

  Kanagawa University

  16 shared

• Yoshiki Hayashi

  Kyushu University

  14 shared

• Eriko Nakato

  University of Minnesota

  13 shared

• Scott B. Selleck

  Pennsylvania State University

  11 shared

• Satoru Kobayashi

  Nagoya University

  9 shared

• Michael B. O’Connor

  University of Minnesota

  8 shared