Dynamic formation of microvillus inclusions

In an international collaboration Mosa and colleagues of AG Farin have now taken advantage of the 3D intestinal organoid model to study MVID. Human mutations in the MUNC18-2/STXBP2 protein cause various degrees of MVID. Using mouse mutant organoids it could now be demonstrated that the intestinal cell differentiation is a key factor for this variability. MVIs could be induced in vitro in a synchronous and highly efficiently manner, which has not been achieved in previous cellular models. By time-lapse microscopy the process of MVIs formation could be visualized for the first time. This revealed that MVIs can form in the cytoplasm or by plasma membrane invagination. The described assays and protocols could improve diagnosis of MVID using patient-derived organoids and might offer a platform to test therapeutic interventions.

Mohammed H. Mosa^1,2,3, Ophélie Nicolle^4,§, Sophia Maschalidi^5,6,§, Fernando E. Sepulveda^5,6, Aurelien Bidaud-Meynard⁴, Constantin Menche², Birgitta E. Michels^1,2,3,7 , Grégoire Michaux⁴*, Geneviève de Saint Basile^5,6,8,#,* and Henner F. Farin^1,2,3,#,*

¹German Cancer Consortium (DKTK), Germany; ²Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany; ³German Cancer Research Center (DKFZ), Heidelberg, Germany; ⁴University Rennes, CNRS, IGDR UMR6290, Rennes, France; ⁵INSERM UMR1163, Laboratory of Normal and Pathological Homeostasis of the Immune system, Paris, France; ⁶Paris Descartes University-Sorbonne Paris Cité, Imagine Institute, Paris, France; ⁷Faculty of Biological Sciences, Goethe University Frankfurt, Germany.?⁸Centre d’Etudes des Déficites Immunitaires, Assistance Publique-Hôpitaux de Paris, France; ^§ Equal contribution; ^#Last authors

*Corresponding Authors Grégoire Michaux: gregoire.michaux@univ-rennes1.fr | Geneviève de Saint Basile: genevieve.de-saint-basile@inserm.fr | Henner F. Farin: farin[at]gsh.uni-frankfurt.de