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 in the same shape even in the presence of internal fluctuations and external perturbations (developmental robustness). Adult tissues also maintain a stable morphology while replacing old or damaged cells with new healthy cells (tissue homeostasis).
but its dysregulation is involved in various diseases. We are focusing common ground between "developmental robustness" and "tissue homeostasis" and regard it as "Morphostasis". Specifically, using a zebrafish as a model animal which issuitable for in vivo imaging analysis of cell-cell communication
and t issue dynamics and genetic analysis, we are exploring unknown molecular systems supporting developmental robustness and testing their potential roles in adult t issue homeostasis and their dysregulation in disease. We try to combine developmental biology and disease study to establish
a new concept of tissue homeostasis.
Aging programs and their regulation
We are tackling the exploration of the molecular mechanisms underlying individual aging. Aging mechanisms have been studied using worm (C.elegans) and fly (Drosophila)as model animals because their life spans are very short . However, their organs are quite different from those of human. In addit
ion, the life spans of mouse and zebrafish, which are well used as human disease model, are very long (3-4yearsl. So, researchers have been searching for short-lived vertebrates. Our lab is using a short-lived fish "turquoise killifish" (the life span of which is 3-6monthsl as a new aging model. This fish
shows age-dependent decline of motility, fertility, and cognitive function, similar to human. We are challenging the clarification of human aging mechanisms and the development of new technique extending "healthy life expectancy" , using turquoise killifish!
- Prof.: Tohru Ishitani
- Asst. Prof.: Yuki Akieda
- Asst. Prof.: Masayuki Oginuma
- SA Asst. Prof.: Shizuka Ishitani
- SA Asst. Prof..: Kota Abe
- JSPS Postdoc.: Kana Aoki
- (1)De novo non-synonymous CTR9 variants are associated with motor delay and macrocephaly: human genetic and zebrafish experimental evidence.
Suzuki et al., Hum Mol Genet. (2022) 31(22):3846-3854.
(2) Rapid reverse genetics systems for N. furzeri, a suitable model organism to study vertebrate aging. Oginuma M., et al., Scientific Reports (2022) 12: 11628
(3) Zebrafish imaging reveals additional TP53 mutation switching oncogene-induced senescence from suppressor to driver in primary tumorigenesis. Haraoka Y., et al., Nature Commun. (2022) 13:1417
(4) Intracellular pH controls WNT downstream of glycolysis in amniote embryos. Oginuma M., et al., Nature (2020) 584(7819):98-101.
(5) Pathogenesis of CDK8-associated disorder: two patients with novel CDK8 variants and in vitro and in vivo functional analyses of the variants. Uehara T., Sci Rep. (2020) 10(1):17575.
(6) Cell competition corrects noisy Wnt/β-catenin morphogen gradients to achieve robust patterning in the zebrafish embryo. Akieda Y., et al., Nature Commun. (2019)10: 4710
(7) 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
(8) 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
(9) 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
(10) Nemo-like kinase suppresses Notch signalling by interfering with formation of the Notch active transcriptional complex. Ishitani T., et al., Nature Cell Biol. (2010) 12:278-85
- Ishitani Lab