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Ghazimoradi, M. H.

Publications and source records attributed to Ghazimoradi, M. H..

2 recordsLinked to original sources

Developmental remodeling of ping-pong piRNA amplification in the vertebrate female germline

The piRNA pathway silences transposable elements (TEs) in the germline, and the ping-pong amplification cycle is the hallmark of this defense.In the male germline, ping-pong is most active during a meiotic window of spermatogenesis, yet its developmental profile in the vertebrate female germline remains less well explored. Most profiling has used adult ovary and mature oocytes, stages at which piRNA pathway components are reported to be low. To address this, we generated matched strand-specific RNA-seq and small RNA-seq from pre-meiotic (E10.5) and meiotic entry (E16.5) chicken ovary, used published single-cell data to track germ-cell composition across the same window, and extended the analysis to the mature chicken ovary and to zebrafish across developmental stages. Ping-pong amplification increases at meiotic entry compared to the pre-meiotic stage across TE classes. In the mature ovary, the signature weakens, and the remaining ping-pong pairs are preferentially associated with LTR/ERV retroelements. We show that activation of a meiotic entry transcriptional program in an in vitro chicken primordial germ cell model increases the fraction of piRNA-sized reads with a partner exhibiting a 10-nt 5' overlap and increases the 1U signature of piRNA-sized reads, consistent with meiotic priming promoting piRNA biogenesis. The zebrafish ovary shows a similar meiosis-associated amplification and preferential targeting of LTR/ERV retroelements at maturity, while carrying roughly 5.7-fold more TE sequences. Similar patterns in two lineages that diverged approximately 430 million years ago suggest that germline development shapes both the timing of ping-pong amplification and the TE classes preferentially associated with it.

developmental biology↗

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↗