bioRxiv Science⌕ Search

bioRxiv · 10.1101/2025.11.10.687746

Stationary and germ layer-specific cellular flows shape the zebrafish gastrula

Abstract

During gastrulation, a sequence of complex processes transforms the blastula into a multi-layered embryo. Fixed sample analysis has revealed much about how genetic signaling cascades determine the major body axes and organize cell fate patterns into the germ layers: ectoderm, mesoderm, and endoderm. In toto live imaging of vertebrate development highlights that embryogenesis is a dynamic process that involves on the order of ten thousand cells, but hurdles related to data handling have hampered quantitative analysis. Therefore, our understanding of the rich physical aspects of multilayered tissue reconfigurations remains incomplete. Here, we reveal that modules of stationary and germ-layer-specific tissue flows shape the zebrafish gastrula. We combine in toto live imaging with tissue-specific markers and image analysis to reveal the global shape of the enveloping layer (EVL), epiblast, and mesoderm over time. A user-friendly tissue cartography pipeline based on the Blender 3D software moves into the reference frame of individual tissue layers. We find distinct tissue flow patterns in the enveloping layer (EVL), epiblast, and mesoderm, respectively. The instantaneous tissue flow of these germ layers is organized in a temporal sequence of hours-long, constant flow patterns. This suggests that a sequence of stationary tissue flow modules transports cells to their destination during gastrulation. Mathematical decomposition suggests that epiblast flow is strongly influenced by a superposition of rotational flow in the mesoderm, and divergent flow in the EVL. Molecular and cellular complexity notwithstanding, these results hint at surprisingly, tractable physical processes that underlie vertebrate gastrulation, and set the stage for investigations of how morphogens orchestrate dynamics.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Wopat, S., Derksen, P., Jain-Sharma, V., Han, G., Claussen, N. H., Streichan, S. J.. 2025-11-12. Stationary and germ layer-specific cellular flows shape the zebrafish gastrula. https://doi.org/10.1101/2025.11.10.687746

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A bicistronic Aldh1a3-P2A-TagBFP knock-in reporter mouse line for studying genitourinary tract development

Aldehyde dehydrogenase 1a3 (Aldh1a3) is an enzyme involved in retinoic acid synthesis with dynamic expression patterns during development, including in the urogenital system. Here, we generated a bicistronic Aldh1a3-P2A-TagBFP knock-in mouse using CRISPR/Cas9 genome editing, inserting TagBFP immediately upstream of the endogenous Aldh1a3 stop codon. Correct targeting was confirmed by Oxford Nanopore long-read sequencing, and heterozygous and homozygous mice were viable and fertile without overt morphological abnormalities. TagBFP fluorescence faithfully overlapped with endogenous Aldh1a3 immunoreactivity and reproduced established expression domains in the developing craniofacial region, intestine, kidney, and broader urogenital system. Extensive characterization of the urogenital system revealed dynamic, spatially restricted BFP reporter activity in Aldh1a3-expressing domains across several key structures, including the ureteric bud and collecting duct lineage, seminal vesicles, caput epididymis, and developing uterine horns. The Aldh1a3-P2A-TagBFP mouse provides a fluorescent resource for visualizing Aldh1a3 expression across development and in adult tissues, including for the characterization of Aldh1a3-expressing domains in the urogenital system. The relatively low fluorescence intensity of TagBFP should be considered when assessing low-level reporter expression.

developmental biology↗

Translation of a small upstream open reading frame functions as a rheostat for the regulation of lin-41 by the Let-7 microRNA in Caenorhabditis elegans

MicroRNAs have been likened to the "dark matter" of eukaryotic genomes, reflecting their pervasive regulatory influence. MicroRNAs were first identified through genetic studies of developmental timing in the nematode Caenorhabditis elegans. Let-7 was the first microRNA recognized to be broadly conserved. The principal target of Let-7 in the developmental timing pathway is the TRIM-NHL RNA-binding protein LIN-41. During the L4 larval stage, Let-7 represses lin-41 translation by binding to two Let-7 complementary sites in the lin-41 3'UTR. Despite the importance of microRNA-based translational regulation, the underlying molecular mechanisms are incompletely understood. Through genetic analysis, we discovered an unrecognized feature of the mechanism by which Let-7 controls lin-41 translation. This mechanism requires a 5'-regulatory exon containing a seven-amino acid upstream open reading frame (uORF) and conserved sequence elements. Genome editing indicates that the specific uORF amino acid sequence itself is not important. Our data suggest that uORF translation and 5'UTR structure limit initiation at the downstream lin-41 start codon, enabling tight control by Let-7. Without this mechanism, the Let-7 microRNA is unable to properly regulate lin-41 to enable proper development.

developmental biology↗

Ductal myofibroblasts reactivate contractile program to stabilize alveolar architecture during lung regeneration

The alveolar sac architecture is essential for efficient gas exchange and must be precisely maintained throughout life; however, how this delicate structure is preserved during adult regeneration remains poorly understood. Using a mouse pneumonectomy model, we found that Lgr6+ Hhip+ ductal myofibroblasts, a poorly characterized mesenchymal population, are indispensable for maintaining alveolar integrity during lung regrowth. Comprehensive characterization using single-cell transcriptomics, mouse genetics, and pharmacological assays demonstrated that these ductal myofibroblasts secrete myogenic factors, most notably CCN4, to reactivate a myogenic program that converts them into contractile PA-DMFs, thereby preserving alveolar architecture. Lineage-tracing further revealed that these ductal myofibroblasts originate from embryonic MCAM- SMA+ distal progenitors via subepithelial TGF-{beta} signaling, serving as a lifelong guardian of alveolar structural integrity. Notably, cross-species analysis identified an analogous population of LGR6+ fibromyocytes in human respiratory bronchioles. Together, these findings indicate ductal myofibroblasts as a developmentally programmed cell population that reactivate a contractile program to structurally support the regeneration of adult lungs.

developmental biology↗