We’re proud to present our #preprint, where we induce embryo-like morphogenesis in #gastruloids, resulting in the generation of trunk-like-structures (#TLS) with #somites flanking the #neuraltube @MPI_MolGen w/ @adrianobolondi . A short summary (1/12) biorxiv.org/content/10.110…
#Gastruloids are a fantastic culture system, but lack proper morphogenesis, e.g. neural cells do not form a neural tube and presomitic mesoderm does not condense into somites. Can we induce proper embryo-like morphology by mechano-chemical manipulation? Yes, we can! (2/12) 
Embedding 96h #gastruloids in 5% #matrigel resulted in trunk-like-structures, with somites flanking the neural tube. Activation of WNT signaling, either alone or in combination with BMP inhibition lead to hyper-epithelialized somites arranged as a bunch of grapes (3/12)
Comparative #RNA-Seq revealed that trunk-like-structures are transcriptionally very similar to #gastruloids, but upregulate genes involved in embryo morphogenesis. Activation of WNT +/- BMP inhibition upregulates somite epithelialization factors (4/12)
A timecourse #scRNAseq analysis of trunk-like-structures revealed the (derivatives of) presomitic mesoderm and neuroectoderm flanking #neuromesodermal progenitors (#NMPs). Also, endoderm, endothelial cells and primordial germ cell like cells (PGCLCs) were present (5/12)
#RNAVelocity (@GioeleLaManno) confirmed that neural and somitic trajectories are rooted in #NMPs. Both trajectories reflect the genetic cascades observed in the #embryo in space and time. (6/12)
For the #devbio aficionados there are many more details in the preprint, e.g. somite polarity, #Hox collinearity #InHoxWeTrust, neural tube cell types, PGCLCs in close contact with the gut-like-structure, ... (7/12)
Mapping of trunk-like-structures to an E7.5-E8.5 mouse embryo compendium revealed high accordance of TLS and embryonic cell types. Taken together, our #scRNAseq analyses demonstrate that TLS execute gene-regulatory programs in an embryo-like spatiotemporal order (8/12)
Can we model a classic #devbio mutant phenotype at the morphological level? Yes! Tbx6 mutant trunk-like-structures fail to form somites and generate ectopic neural tubes, thus mirroring the embryonic mutant phenotype #InTLSWeTrust ;) (9/12)
Somitogenesis in #TLS can occur at an embryo-like-pace. This is in line with a beautiful recent study in @nature by @AlexandervanOu1 @SusannevdBrink @AMartinezArias @annionna @_Hubrecht that shows an in-vivo-like #segmentation clock and somitogenesis in #gastruloids. (10/12)
In sum, we demonstrate that the morphogenetic potential of #gastruloids is unlocked by providing an ECM surrogate and that the resulting #TLS constitute a scalable and tractable platform for investigating lineage decisions and morphogenetic processes shaping the embryo (11/12)
This #preprint wouldn’t be there without my brilliant and gifted colleagues at the @MPI_MolGen, in particular @adrianobolondi , @helene_whoever , Leah Haut, @d_schifferl, Bernhard Herrmann and Alexander Meissner. Lots of questions remain which we’re dying to answer! (12/12)
