Prof. Dr. Didier Stainier
MPI for Heart and Lung Research, Department of Developmental Genetics
The Department of Developmental Genetics investigates questions related to organogenesis including cell differentiation, tissue morphogenesis, organ homeostasis and function, as well as organ regeneration. We study these questions in zebrafish as well as in mouse and are currently looking at several mesodermal (heart, vasculature) and endodermal (lung) organs. We utilize both forward and reverse genetic approaches, and aim to dissect cellular processes using high-resolution live imaging. One goal of our studies is to gain understanding of vertebrate organ development at the single-cell level, and beyond.
1) Cardiac development and regeneration
Projects aim to understand key aspects of cardiac development including trabeculation and valve formation at single cell resolution. Other projects delve into relatively unexplored areas of cardiac regeneration including the role of the immune system.
Jiménez-Amilburu V, Rasouli SJ, Staudt DW, Nakajima H, Chiba A, Mochizuki N and Stainier DY (2016). In Vivo Visualization of Cardiomyocyte Apicobasal Polarity Reveals Epithelial to Mesenchymal-like Transition during Cardiac Trabeculation. Cell Reports 17, 687-2699.
Lai SL, Marín-Juez R, Moura PL, Kuenne C, Lai JKH, Tsedeke AT, Guenther S, Looso M and Stainier DYR (2017). Reciprocal analyses in zebrafish and medaka reveal that harnessing the immune response promotes cardiac regeneration. eLife 25605.
Marín-Juez R, El-Sammak H, Helker CSM, Kamezaki A, Mullapudi ST, Bibli SI, Foglia MJ, Fleming I, Poss KD and Stainier DYR (2019). Coronary revascularization is regulated by epicardial and endocardial cues and forms a scaffold for cardiomyocyte repopulation. Developmental Cell 51, 503-515.
Gunawan F, Gentile A, Fukuda R, Tsedeke AT, Jiménez-Amilburu V, Ramadass R, Iida A, Sehara-Fujisawa A and Stainier DYR (2019). Focal adhesions are essential to drive zebrafish heart valve morphogenesis. J Cell Biol. 218, 1039-1054.
Priya R, Allanki S, Gentile A, Mansingh A, Uribe V,Maischein HM, Stainier DYR (2020). Tension heterogeneity directs form and fate to pattern the myocardial wall. Nature 2020 Dec;588(7836):130-134
2) Vascular development
Projects aim to understand endothelial cell differentiation and behavior in the context of blood vessel formation in zebrafish and mouse.
Vanhollebeke B, Stone OA, Bostaille N, Cho C, Zhou Y, Maquet E, Gauquier A, Cabochette P, Fukuhara S, Mochizuki N, Nathans J and Stainier DY (2015). Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis. eLife 06489.
Reischauer S, Stone O, Villasenor A, Chi N, Jin SW, Martin M, Lee MT, Fukuda N, Marass M, Witty A, Fiddes I, Kuo T, Chung WS, Salek S, Lerrigo R, Alsiö J, Luo S, Tworus D, Augustine SM, Mucenieks S, Nystedt B, Giraldez AJ, Schroth GP, Andersson O and Stainier DY (2016). Cloche is a bHLH-PAS transcription factor that drives hemato-vascular specification. Nature 535, 294-298.
Gerri C, Marín-Juez R, Marass M, Marks A, Maischein HM and Stainier DYR (2017). Hif-1α regulates macrophage-endothelial interactions during blood vessel development in zebrafish. Nature Communications 8, 15492.
Marass M, Beisaw A, Gerri C, Luzzani F, Fukuda N, Günther S, Kuenne C, Reischauer S and Stainier DYR (2019). Genome-wide strategies reveal target genes of Npas4l associated with vascular development in zebrafish. Development 146, dev173427.
Boezio GLM, Bensimon-Brito A, Piesker J, Guenther S, Helker CSM, Stainier DYR (2020). Endothelial TGF-β signaling instructs smooth muscle cell development in the cardiac outflow tract. eLife 9:e57603
3) Genetic compensation and transcriptional adaptation
The goal of this project is to define the molecular mechanisms underlying the broadly reported but poorly understood phenomena of genetic compensation and transcriptional adaptation.
Rossi A, Kontarakis Z, Gerri C, Nolte H, Hölper S, Krüger M and Stainier DY (2015). Genetic compensation induced by deleterious mutations but not gene knockdowns. Nature 524, 230-233.
El-Brolosy MA and Stainier DYR (2017). Genetic compensation: A phenomenon in search of mechanisms. PLoS Genet. 13, e1006780.
El-Brolosy MA, Kontarakis Z, Rossi A, Kuenne C, Günther S, Fukuda N, Kikhi K, Boezio GLM, Takacs CM, Lai SL, Fukuda R, Gerri C, Giraldez AJ and Stainier DYR (2019). Genetic compensation triggered by mutant mRNA degradation. Nature 568, 193-197.
Jakutis G and Stainier DYR (2021). Genotype-Phenotype Relationships in the Context of Transcriptional Adaptation and Genetic Robustness. Annu Rev Genet. doi: 10.1146/annurev-genet-071719-020342. Online ahead of print.