No Nodal? No problem! Initiation and maintenance of the pluripotent epiblast in pre-implantation human development is independent of NODAL signaling. Beatiful work hot off the press from @asbrumm.bsky.social www.cell.com/developmenta... #DevBio - ThreadSky

cellysally.bsky.social • 189 days ago

No Nodal? No problem!

Initiation and maintenance of the pluripotent epiblast in pre-implantation human development is independent of NODAL signaling.

Beatiful work hot off the press from @asbrumm.bsky.social

https://www.cell.com/developmental-cell/fulltext/S1534-5807(24)00639-7

#DevBio

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doctoremmerson.bsky.social•188 days ago

Congratulations @asbrumm.bsky.social 🥳

asbrumm.bsky.social•91 days ago

A lay summary of this work is now available: https://hdbi.org/human-epiblast-pluripotency-is-nodal-independent

Special thanks once again to Kathy @niakanlab.bsky.social and Richard Acton at @babrahaminst.bsky.social

asbrumm.bsky.social•188 days ago

Thank you so much @cellysally.bsky.social - great slogan!
I'll cross-post my Twitter thread below.

asbrumm.bsky.social•188 days ago

In my PhD work, published last Monday, we show that both NODAL and BMP signalling are active in the human blastocyst, but NODAL signalling is not required to initiate or maintain the human pluripotent epiblast. 1/10

asbrumm.bsky.social•188 days ago

In vitro, NODAL regulates pluripotency, by promoting NANOG expression, as shown by Ludovic Vallier, AnnaOsnato and others. We thus wondered whether NODAL signalling activity was active in pre-implantation human development and involved in human pluripotency in vivo. 2/10

asbrumm.bsky.social•188 days ago

To characterise NODAL signalling activity, we optimised an immunofluorescence protocol to detect the intracellular effectors SMAD2/3, which become phosphorylated and accumulate in the nucleus upon ligand binding. See also Kruger et al https://doi.org/10.1242/dev.202377 3/10

asbrumm.bsky.social•188 days ago

We found that NANOG expression emerges in the inner cell mass of human blastocysts at 5 days post fertilisation, in the absence of NODAL signalling activity. NODAL signalling then becomes active throughout the pluripotent epiblast and extra-embryonic primitive endoderm. 4/10

asbrumm.bsky.social•188 days ago

We next characterised three NODAL signalling inhibitors, yet only A8301 reliably inhibited SMAD2/3 phosphorylation and nuclear accumulation. The required high concentration of A8301 also inhibited BMP signalling, found in the primitive endoderm of human blastocysts. 5/10

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