Ishitani Lab/Division of Cellular and Molecular Biology  Department of Homeostatic regulation

In our body, cells recognize their position and role and behave accordingly via cell-cell communication. Such behavior supports tissue morphogenesis and homeostasis, while its dysregulation is involved in congenital malformation, cancer, degenerative diseases, and aging. We focus especially on the cell-cell communication and behavior supporting tissue homeostasis and explore unknown molecular systems controlling embryonic development, organogenesis, regeneration, aging, and disease, using in vivo imaging, animal model genetics, molecular and cell biology, and biochemistry techniques.

A new concept of tissue homeostasis “Morphostasis”

Developing animal tissues are reproducibly formed, even in the presence of internal fluctuations and external stressors (developmental robustness). Adult tissues also maintain a stable morphology while replacing old or damaged cells with new healthy cells (tissue homeostasis). However, dysregulation of these processes is involved in various diseases. We are focusing on the common ground between “developmental robustness” and “tissue homeostasis,” which we term as “morphostasis.” Specifically, using a zebrafish animal model for in vivo imaging analysis of cell-cell communication, tissue dynamics and genetic analysis, we explore unknown molecular systems that support developmental robustness and test their potential roles in adult tissue homeostasis and their dysregulation during disease. We aim to combine developmental biology and pathology to establish a new concept of tissue homeostasis.

Aging programs and their regulation

We are exploring the molecular mechanisms underlying individual aging. Aging mechanisms have been studied using worms (C. elegans) and fruit flies (Drosophila) as animal models because their life spans are very short. However, their organs are quite different from those of humans. Conversely, the life spans of mice and zebrafish, which are commonly used to model human disease, are long (3 - 4 years). So, researchers have been searching for short-lived vertebrates to use as animal models of disease. Our laboratory is using a short-lived fish, “turquoise killifish” (the life span of which is 3 - 6 months), as a new model for aging. This fish shows age-dependent decline of motility, fertility, and cognitive function, similar to that seen in humans. We are clarifying the mechanisms of human aging and developing new techniques for extending “healthy life expectancy,” using turquoise killifish!

Staff

  • Prof.: Tohru Ishitani
  • Assis. Prof.: Yuki Akieda
  • Assis. Prof.: Masayuki Oginuma
  • SA Asst. Prof.: Shizuka Ishitani
  • Postdoc.: Kota Abe

Website

Publications

  • (1) Cell competition corrects noisy Wnt morphogen gradients to achieve robust patterning in the zebrafish embryo. Akieda Y. et al. Nature Commun. (2019)10: 4710
    (2) Horizontal Boundary Cells, a Special Group of Somitic Cells, Play Crucial Roles in the Formation of Dorsoventral Compartments in Teleost Somite. Abe K. et al. Cell Rep. (2019) 27:928-939
    (3) Hipk2 and PP1c cooperate to maintain Dvl protein levels required for Wnt signal transduction. Shimizu N., et al., Cell Reports (2014) 8(5) 1391-1404
    (4) Visualization and exploration of Tcf/Lef function using a highly responsive Wnt/β-catenin signaling-reporter transgenic zebrafish. Shimizu N., et al., Developmental biology (2012) 370(1) 71-85
    (5) NLK positively regulates Wnt/β-catenin signalling by phosphorylating LEF1 in neural progenitor cells. Ota S., et al., EMBO Journal (2012) 31:1904-15
    (6) Nemo-like kinase suppresses Notch signalling by interfering with formation of the Notch active transcriptional complex. Ishitani T., et al., Nat. Cell Biol. (2010) 12:278-85
    (7) Nrarp functions to modulate neural-crest-cell differentiation by regulating LEF1 protein stability. Ishitani T., et al., Nat. Cell Biol. (2005) 7:1106-12
    (8) The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and transcription factor TCF. Ishitani T., et al., Nature (1999) 399:798-802