Sheri

Our lab is obsessed by hidden biology - protein products central to understanding how our cells function, but missing from standard genome annotations. Introducing new work from post-doc Eric Smith on alternative translational isoforms for heterochromatin protein 1. www.biorxiv.org/content/10.6...

Always a pole cell never a pgc! Transcription may be essential to segregate healthy and defective pole cells. Pole cells that never activate their zygotic genome and retain what mommy gave them, die. Pole cells that activate their zygotic genome too much also die. Life is a balance! 8/8

Lost children are the first germ cells to die during embryogenesis, they fail to undergo trans-epithelial migration and are lost in the gut. When we rescue their death with chk2 mutants they still retain maternal transcripts and do not express zygotic transcripts. 7/8

Finally, our data uncovered a second unexpected cluster of germ cells that we term lost children. These germ cells are isolated from the 9 to 12 hour AEL window as coalesced germ cells. These germ cells completely retain their maternal transcriptome and never activate zygotic gene expression. 6/8

As It turns out, nanos actually inhibits Zelda protein levels in pole cells! Now we find that pole cells in nanos mutants have a dramatic increase in Zelda protein. Nanos -> Zelda -> class II genes. This sheds new light for how nanos protects germline identity and prevents its somatization. 5/8

We found that while these class II genes are expressed in pole cells, their translation is inhibited by nanos. Unexpectedly, when we examined class II transcription in nanos mutants we found a dramatic increase in their transcription!! 4/8

Instead, their transcription is dependent on the pioneer factor #Zelda, where loss of Zelda results in loss of early pole cell transcription. 3/8

This work would not have been possible without the incredible snATAC-seq atlas of the Drosophila embryo from @diegoisworking.bsky.social @jshendure.bsky.social and @eileen-furlong.bsky.social which helped us discover that germ cells retain a totipotent chromatin state throughout development!

Thank you @arjunarajakumar.bsky.social Couldn't have done it without you!