Corazza, S. | Search bioRxiv

bioRxiv2026

BMP2 signaling cooperates with retinoic acid to activate a meiotic-entry transcriptional program in chicken primordial germ cells

The initiation of meiosis in germ cells is largely regulated by extrinsic cues from the gonadal environment, but the logic of these signals remains poorly understood in non-mammalian vertebrates. Retinoic acid has long been considered a principal meiosis-inducing signal, yet recent genetic and reconstitution studies indicate that retinoic acid alone is insufficient. In mice, bone morphogenetic protein 2 cooperates with retinoic acid to establish the oogenic program through the bone morphogenetic protein-responsive transcriptional regulator Zglp1, but whether this regulatory logic is conserved beyond mammals is unknown. Here, using cultured chicken (Gallus gallus) primordial germ cells, we show that bone morphogenetic protein 2 cooperates with retinoic acid to promote a meiotic-entry transcriptional program. Retinoic acid alone induced a limited retinoic acid-responsive state, whereas combined treatment reduced the primordial germ cell program and activated early meiotic genes. The resulting transcriptome matched the premeiotic-to-meiotic-entry transition of the embryonic ovary in a single-cell atlas of chicken germ cells. We also generated a genome-edited primordial germ cell line carrying an SYCP3 promoter-green fluorescent protein reporter as a platform for dissecting meiotic-entry signals in culture. Comparative genomic analysis revealed Gallus-specific pseudogenization of ZGLP1, which is intact in closely related galliform species. Retinoic acid and bone morphogenetic protein may therefore act through a different downstream regulator in chicken. Article summaryEggs and sperm are produced by meiosis, a specialized cell division that starts during embryonic development. Retinoic acid, a signal derived from vitamin A, was long thought to be enough to start meiosis, but on its own it is not. In mice, a second signal, bone morphogenetic protein 2 (BMP2), works alongside retinoic acid to push germ cells toward the egg-producing program. We asked whether birds use the same combination. Giving both signals to chicken primordial germ cells in culture switched on genes for egg development and for the first steps of meiosis; retinoic acid alone did not. Birds and mammals last shared an ancestor more than 300 million years ago, so the pairing of these two signals appears to be an old feature of vertebrate germ cells. The cells stopped short of completing meiosis, which means other signals are still missing. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=169 SRC="FIGDIR/small/740788v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@10b8b22org.highwire.dtl.DTLVardef@db9a08org.highwire.dtl.DTLVardef@15d9726org.highwire.dtl.DTLVardef@16e4dd3_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2024

Ancient genomics support deep divergence between Eastern and Western Mediterranean Indo-European languages

The Indo-European languages are among the most widely spoken in the world, yet their early diversification remains contentious1-5. It is widely accepted that the spread of this language family across Europe from the 5th millennium BP correlates with the expansion and diversification of steppe-related genetic ancestry from the onset of the Bronze Age6,7. However, multiple steppe-derived populations co-existed in Europe during this period, and it remains unclear how these populations diverged and which provided the demographic channels for the ancestral forms of the Italic, Celtic, Greek, and Armenian languages8,9. To investigate the ancestral histories of Indo-European-speaking groups in Southern Europe, we sequenced genomes from 314 ancient individuals from the Mediterranean and surrounding regions, spanning from 5,200 BP to 2,100 BP, and co-analysed these with published genome data. We additionally conducted strontium isotope analyses on 224 of these individuals. We find a deep east-west divide of steppe ancestry in Southern Europe during the Bronze Age. Specifically, we show that the arrival of steppe ancestry in Spain, France, and Italy was mediated by Bell Beaker (BB) populations of Western Europe, likely contributing to the emergence of the Italic and Celtic languages. In contrast, Armenian and Greek populations acquired steppe ancestry directly from Yamnaya groups of Eastern Europe. These results are consistent with the linguistic Italo-Celtic10,11 and Graeco-Armenian1,12,13 hypotheses accounting for the origins of most Mediterranean Indo-European languages of Classical Antiquity. Our findings thus align with specific linguistic divergence models for the Indo-European language family while contradicting others. This underlines the power of ancient DNA in uncovering prehistoric diversifications of human populations and language communities.

genetics↗