Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2021.09.30.462471

Bioactive isoprenoids guide migrating germ cells to the embryonic gonad

Barton, L.·Sanny, J.·Dawson, E. P.·Nouzova, M.·Noriega, F. G.·Stadtfeld, M.·Lehmann, R.
View original source ↗Export metadata ↓

Abstract

Germ cells are essential to sexual reproduction. Across the animal kingdom, extracellular signaling isoprenoids, such as retinoic acids (RAs) in vertebrates and juvenile hormones (JHs) in invertebrates, facilitate multiple processes in the germline lifecycle. Here we investigated the role of these potent signaling molecules in embryonic germ cell migration, using JHs in Drosophila melanogaster as a model system. In contrast to their established endocrine roles during larval and adult germline development, we found that JH signaling acts locally during embryonic development. Using an in vivo biosensor, we found JH signaling is first active near primordial germ cells (PGCs) as they migrate to the developing somatic gonad. Through in vivo and in vitro assays, we found that JHs are both necessary and sufficient for PGC migration. Analysis into the mechanisms of this newly uncovered paracrine JH function revealed that PGC migration was compromised when JHs were reduced or increased, suggesting that specific titers or spatiotemporal JH dynamics are required for robust PGC colonization to the gonad. Compromised PGC migration can impair fertility and cause germ cell tumors in many species, including humans. In mammals, retinoids, a JH-related family of signaling isoprenoids, has many roles in development and reproduction. We found that retinoic acid, like JH, was sufficient to impact PGC migration in vitro. Together, our study reveals a previously unanticipated role of isoprenoids as local effectors of pre-gonadal PGC development and suggests a broadly shared mechanism in PGC migration. HighlightsO_LIJuvenile hormones (JH) are necessary & sufficient for Primordial Germ Cell (PGC) migration. C_LIO_LIJH signaling acts directly in and around migrating PGCs prior to its endocrine function. C_LIO_LICompensatory feedback sensitive to JH receptor function maintains JH homeostasis. C_LIO_LIJH-like retinoic acids may have similar roles during mammalian germ cell migration. C_LI

Explore related subjects

developmental biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Barton, L., Sanny, J., Dawson, E. P., Nouzova, M., Noriega, F. G., Stadtfeld, M., Lehmann, R.. 2021-10-01. Bioactive isoprenoids guide migrating germ cells to the embryonic gonad. https://doi.org/10.1101/2021.09.30.462471

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↗