bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.03.09.483697

Thymus formation in uncharted embryonic territories.

Alcobia, I.·Gama-Carvalho, M.·Magalhaes, L.·Proa, V.·Henrique, D.·Neves, H.
View original source ↗Export metadata ↓

Abstract

The thymus is a conserved organ among vertebrates, derived from the endoderm of distinct pharyngeal pouches (PP), whose location and number vary across species. Together with reports of sporadic ectopic thymus locations in mice and humans, this suggests that the potential to make a thymus resides in a broader region of the PP endoderm than previously ascribed. Using the chick-quail chimera system, we explore this hypothesis and test the capacity of non-canonical pouches to participate in thymus formation. We further ask if the local mesenchyme of pharyngeal arches (PA) could also play a role in the regulation of thymus formation. After testing several embryonic tissue associations, we mapped the pharyngeal endoderm regions with thymus potential to the second and third/fourth pharyngeal pouches (2PP and 3/4PP). We further identified mesenchyme regions that regulate this potential to the 3/4 pharyngeal arches and to the dorsal region of the second arch, with positive and negative influences, respectively. Transcriptomic analysis of these tissues helped us revealing a common genetic program in the PP endoderm linked to thymus potential in addition to finding distinct signalling pathways involved in the cellular interactions with the mesenchyme of the pharyngeal arches that result in modulating this potential. Together, these results provide new information about the initial specification of thymus primordia in the embryo that may contribute to improving the development of thymus organoid systems. GO_SCPLOWRAPHICALC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWABSTRACTC_SCPLOW O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/483697v2_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@a12a67org.highwire.dtl.DTLVardef@e6d49eorg.highwire.dtl.DTLVardef@90d7b0org.highwire.dtl.DTLVardef@140672e_HPS_FORMAT_FIGEXP M_FIG C_FIG

Explore related subjects

developmental biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Alcobia, I., Gama-Carvalho, M., Magalhaes, L., Proa, V., Henrique, D., Neves, H.. 2022-03-11. Thymus formation in uncharted embryonic territories.. https://doi.org/10.1101/2022.03.09.483697

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

KEEP EXPLORING

Related preprints

bioRxiv2026

Hyaluronic acid dynamics are regulated by neural crest cells and NEDD4 in the developing cardiac outflow tract valves

The extracellular matrix (ECM) is essential for cardiac valve development, with hyaluronic acid (HA) playing a critical role in cardiac cushion formation. While HA is required for atrioventricular valve development, its role in semilunar valve formation remains poorly understood. The ubiquitin ligase NEDD4 is essential for cardiac outflow tract development, particularly within cardiac neural crest cells, however its role in semilunar valve development has been unexplored. Here, we demonstrate that neural crest-specific deletion of NEDD4 in mice disrupts outflow tract valve development, resulting in abnormal leaflet number and morphology. Analysis of valve ECM revealed a specific reduction in HA within the neural crest-derived valve mesenchyme, while other ECM components such as fibronectin and versican remained unaffected. In contrast, deletion of NEDD4 in endocardium-derived valve mesenchyme did not alter HA abundance. Using NEDD4-deficient neural crest cells, we further demonstrate a cell-autonomous requirement for NEDD4 in regulating HA abundance, with in vitro evidence supporting impaired HA synthesis rather than increased turnover of HA in the ECM. Our findings identify a previously unrecognised role for NEDD4 in regulating HA synthesis in cardiac neural crest cells, revealing a cell-type-specific mechanism governing semilunar valve development and highlighting distinct cellular requirements for ECM regulation across cardiac valve populations.

developmental biology↗
bioRxiv2026

Endogenous Mechanical Reporters Encode the Global Mechanical Landscape of Morphogenesis

Developmental systems usually comprise multiple genetically programmed morphogenetic events within a mechanically continuous environment, yet how individual processes interact and contribute to the overall mechanical landscape remains unknown. Here, we introduce the concept of mechanical reporter: endogenous tissues function as in situ probes of the embedded mechanical landscape. We exemplified cephalic furrow (CF) migration as a mechanical reporter in gastrulating Drosophila. Using optogenetics and genetics, we revealed that CF displacement reflects the combined effect of both force and tissue mechanical properties. By incorporating condition-specific mechanical landscape into a continuum minimal-response model, we developed a framework to quantitatively predict the reporter dynamics. Using different genetic mutants, we successfully decoded changes in the mechanical landscape from CF dynamics in gastrulating Drosophila. Overall, we established a predictive framework that uses CF dynamics to infer changes in the global mechanical landscape. Beyond this, the concept of mechanical reporter provides a general strategy for systematically understanding and decoding complex mechanical environments in living systems.

developmental biology↗
bioRxiv2026

Dissecting human embryonic patterning during organogenesis reveals a rostral midline progenitor population for mesoendoderm induction

Understanding how human organogenesis is accomplished via intricate spatiotemporal patterning of organ primordia requires spatial atlases at cellular resolution. However, existing human embryo spatial atlases are built using sequencing-based platforms such as Stereo-seq, which have limited spatial resolution and blurred anatomical boundaries, leading to misclassification across adjacent cells. Here, we integrate in situ imaging-based transcriptomics (Xenium) with transcriptome-wide spatial profiling (Visium-HD) of Carnegie stages 9-12 embryos to delineate the patterning of core embryonic tissues at single-cell resolution, including the brain, spinal cord, somites, neural crest, notochord, heart, and gut tube. A new finding enabled by spatial single-cell resolution is the identification of rostral midline progenitors (RMPs), a cell population co-expressing SOX2, TBXT, and OTX2. Transcriptionally, RMPs are distinct from both neuromesodermal progenitors (NMPs) and prechordal mesoderm, and in vivo clonal barcoding in mice indicates that RMPs share a common developmental origin with rostral neural ectoderm. To interrogate their functional significance, we leveraged our spatial transcriptome data to recapitulate RMP-like cells from human pluripotent stem cells and showed that these cells can induce epiblast-like cells to acquire mesendodermal and endodermal fates, while themselves adopting an ectodermal fate consistent with their in vivo counterparts. This work provides a 3D, stage-resolved molecular cell atlas of tissue patterning in human embryo that serves as a reference for in vitro models.

developmental biology↗