Prof. Dr. Didier Stainier

   MPI-HLR, Department III, 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 (pancreas, 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.

 

 

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 as well as cardiac valve regeneration.

 Recent references:

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.

Marín-Juez R, Marass M, Gauvrit S, Rossi A, Lai SL, Materna SC, Black BL and Stainier DY (2016).  Fast revascularization of the injured area is essential to support zebrafish heart regeneration.  Proc Natl Acad Sci USA 113: 11237-11242.

Rasouli SJ and Stainier DYR (2017).  Regulation of cardiomyocyte behavior in zebrafish trabeculation by Neuregulin 2a signaling.  Nature Communications 8: 15281.

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.

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Vascular development

 

Projects aim to understand endothelial cell differentiation and behavior in the context of blood vessel as well as lymphatic vessel formation in zebrafish and mouse.

 Recent references:

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.

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Pancreas development and function

 

Projects aim to understand endocrine cell differentiation and transdifferentiation during development and regeneration and also to identify novel regulators of glucose homeostasis.  Another project looks at the role of innervation in endocrine cell development and function.

References:

Andersson O, Adams BA, Yoo D, Ellis GC, Gut P, Anderson RM, German MS and Stainier DYR (2012).  Adenosine signaling promotes regeneration of pancreatic b-cells in vivo.  Cell Metabolism 15: 885-894. 

Ninov N, Hesselson D, Gut P, Zhou A, Fidelin K and Stainier DYR (2013).  Metabolic control of pancreatic endocrine differentiation.  Current Biology 23: 1242-1250.

Ye L, Robertson MA, Hesselson D, Stainier DYR and Anderson RM (2015).  Glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis.  Development 142: 1407-17.

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Lung development and homeostasis

 

Projects aim to understand lung cell differentiation and morphogenesis as well as lung homeostasis and mostly started with a forward genetic screen using ENU mutagenesis.

References:

Yin W, Kim HT, Wang SP, Gunawan F, Wang L, Buettner C, Grohmann B, Graef V, Zhong H, Roman D, Preussner J, Guenther S, Looso M, Mardon G, Offermanns S and Stainier DYR.  The potassium channel KCNJ13 is essential for smooth muscle cytoskeletal organization during mouse tracheal tube formation.  Submitted.

Kim HT, Yin W, Jin YJ, Gunawan F, Grohmann B, Buettner C, Sokol AM, Preussner J, Guenther S, Kostin S, Ruppert C, Bhagwat AM, Ma X, Graumann J, Looso M, Guenther A, Offermanns S, Adelstein RS and Stainier DYR.  Myh10 deficiency leads to defective ECM remodeling and pulmonary disease.  Submitted.

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Genetic compensation and transcriptional adaptation

 

The goal of this project is to understand molecular mechanisms underlying the broadly reported but poorly understood phenomena of genetic compensation and transcriptional adaptation.

References:

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.

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For additional references of our work, please see

https://www.ncbi.nlm.nih.gov/pubmed/?term=stainier+d

© 2018 Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany