Evolution has brought about diverse body forms which would fit with ecological needs of the species. For example, humans have much longer legs compared to any other extant primates, which enables our unique upright bipedality and has presumably allowed our large brain to be evolved. However, not much is known about how those species-specific shapes are encoded in genomes.
In order to pursuit that question, I have been studying comparative developmental biology. Recently, growing number of species has been established as model organisms for comparative studies of development and morphogenesis. Advance in sequencing technologies and genome editing technologies such as CRISPR has allowed us to explore molecular and genetical differences among different species. However, traditional model species, such as mouse, zebrafish, and fruit fly became popular as models largely because their ecological and physiological features are very suitable for laboratory settings and other comparative models are, in many cases, still not as quite experimentally accessible as traditional model animals. Furthermore, it is ethically impermissible to perform invasive experiments on human embryos.
I believe that organoids based on pluripotent stem cells will circumvent some of those problems and provide great opportunities to elucidate developmental and genetical mechanisms of interspecies morphological diversity. It has been demonstrated that many aspects in morphogenesis including species-specificity can be recapitulated in 3-dimensional culture. For example, optic cup organoids from human pluripotent stem cells are larger and thicker, and require longer developmental duration compared to those from mouse cells. If species-specific aspects of morphogenesis are recapitulated in organoids, that would allow invasive analysis such as live imaging and genetic and pharmaceutical manipulations to provide mechanistical insights in moprhogenesis. Furthermore, if the species-specific morphological differences are showed up in organoid in the essentially similar culture conditions, those experiments would highlight cell-autonomous differences and genomic regions which is responsible for species-specific differences.
In ASHBi, we would like to establish in vitro models of growing limb bones which would recapitulate position- and species-specific growth from closely related rodents and primates: mouse and jerboa, human and macaques (Fig 1) we would also like to establish comparative models of eye cup organoids from closely related rodent species with different eye size: mouse, naked mole rat, and jerboa to understand general mechanisms on how eye size is determined relative to the body size in species specific manner (Fig 2). I hope our work will provide novel insights on “Where Do We Come From? What Are We? Where Are We Going?”
Rio Tsutsumi obtained his PhD (Science) from Kyoto University under supervision of Dr. Kiyokazu Agata in 2015. After having postdoctoral training in Dr. Kimberly Cooper’s lab at University of California, San Diego, US from 2015 to 2019, he joined Dr. Mototsugu Eiraku’s lab at Kyoto University as a postdoc in 2019.
Convergent metatarsal fusion in jerboas and chickens is mediated by similarities and differences in the patterns of osteoblast and osteoclast activities
Gutierrez HL*, Tsutsumi R*, Moore TY, Cooper KL
Evolution and Development 2019 Nov Volume 21, Issue6, Pages 320-329
Evolutionary loss of foot muscle during development with characteristics of atrophy and no evidence of cell death
Tran MP, Tsutsumi R, Erberich JM, Chen KD, Flores MD, Cooper KL
Elife 2019 Oct Volume 8, e50645.
Changing While Staying the Same: Preservation of Structural Continuity During Limb Evolution by Developmental Integration
Tsutsumi R, Tran MP, Cooper KL.
Integrative and Comparative Biology 2017 Dec Volume 57, Issue 6, Pages 1269–1280
Functional joint regeneration is achieved using reintegration mechanism in Xenopus laevis
Tsutsumi R, Yamada S, Agata K.
Regeneration 2016 Feb Volume 3, Issue 1, Pages 26–38
Epigenetic Modification Maintains Intrinsic Limb-Cell Identity in Xenopus Limb Bud Regeneration
Hayashi S, Kawaguchi A, Uchiyama I, Kawasumi-Kita A, Kobayashi T, Nishide H, Tsutsumi R, Tsuru K, Inoue T, Ogino H, Agata K, Tamura K
Developmental Biology 2015 Oct Volume 406, Issue 2, Pages 271–282
Reintegration of the regenerated and the remaining tissues during joint regeneration in the newt Cynops pyrrhogaster
Tsutsumi R, Inoue T, Yamada S, Agata K.
(First/ Co-corresponding author)
Regeneration 2015 Feb Volume 2, Issue 1, Pages 26–36
Lens regenerates by means of similar processes and timeline in adults and larvae of the newt Cynops pyrrhogaster
Inoue T, Inoue R, Tsutsumi R, Tada K, Urata Y, Michibayashi C, Takemura S, Agata K.
Devlopmental Dynamics 2012 Oct Volume 241, Issue 10 Pages 1575–1583
April, 2014-March, 2016 JSPS fellowship and Grant-in-Aid for JSPS fellow Postdoc Poster Award at SDB West Coast Regional Meeting (Mar 2017)