Fatima Batool et al. show how enhancers work together with transcription factors to turn on specific genes in the developing brain and follow a set of rules to make sure the right genes are activated in the human forebrain. 🧠 doi.org/10.1242/bio....

Your daily (baby) Mochi!
#hbd #hes5

Using in-vitro neural progenitor cultures and timelapse imaging, we show that most cells are in a hybrid HES1/HES5 state characterised by co-oscillation at a common 3-4h period. At the same time, a minority of progenitors show resolution of the hybrid state into one dominant HES.

Oscillatory Co-expression of HES1 and HES5 Enables a Hybrid State in a Bistable Transcription Factor Regulatory Motif https://www.biorxiv.org/content/10.1101/2025.05.22.655498v1

In the coupled model, the resolution of the cross-repressive motif into a single dominant HES occurs through a change in cross-repression threshold and/or level; this suggests that a similar process could occur during development to give rise to separate HES1 and HES5 expression domains.

Overall, our exploration of HES1 and HES5 in the same cell suggests that a co-expressing hybrid state is enabled by oscillatory dynamics and synchronisation at single cell level.

Taking it one step further, cKO of α1ARs in a subset of spinal astrocytes (Hes5+) had a similar effect on both NE- or stress-evoked pain hypersensitivity, directly linking NE neuromodulation of astrocyte activity to the effects of stress in pain perception. 5/

Excited to share that my latest preprint! We use dual reporters and computation to explore the bistable HES1-HES5 motif and find that oscillations enable a hybrid state characterised by synchrony of HES1 and HES5 resolving into single HES during the development of mouse embryonic spinal cord.

Watch the "Sertraline" vision quest music video now, directed by Greta Kline of Frankie Cosmos, which imho accurately matches the song's rushing fever dream vibe—special guest appearances by Katie von Schleicher and Ursula.

www.youtube.com/watch?v=hES5...

Oscillatory Co-expression of HES1 and HES5 Enables a Hybrid State in a Bistable Transcription Factor Regulatory Motif #SingleCell 🧪🧬🖥️
https://www.biorxiv.org/content/10.1101/2025.05.22.655498v1

Photo: The birthday boy! #bestday #hes5 #magiccastle #cupcake #coldstone

Finally, tying the whole thing together, A1R antagonism prevented a reduction in inhibitory input onto spinal cord neurons triggered by chemogenetic activation of Hes5+ astrocytes. 9/

Using a computational model of HES protein repressing mRNA, we find that differences in protein stability give them distinct free-running oscillatory periods, but co-expression results in phase-locking, with slower HES5 entraining faster HES1.

The birthday boy! #bestday #hes5 #magiccastle #cupcake #coldstone

If you want to see your 401k retirement fund dying on the vine and disappearing before your eyes, here's the ticker. www.youtube.com/watch?v=HEs5...

In mouse Muller glia, we saw upregulation of gliogenesis-related TFs such as Nfix, Hes5, and Sox9 in aged cells. This may reflect compensatory gliogenic activity. Interestingly, this pattern was absent in humans, which showed weaker age-linked inflammatory shifts./23

How does Flying Frog fly? Genomes from a gliding & non-gliding Rhacophorus showed accelerated evolution linked to limb development in both but expression differences in the WNT signaling pathway => webbing for gliding
(Link shows VIDEO OF GLIDING/ PLUMMETING FROGS!)
#2025MMM
doi.org/10.1073/pnas...

Using in vivo data, we show that the fraction of neural progenitor cells that co-express HES1 and HES5 becomes reduced between E9.5 and E10.5. This is supported by analysis of existing transcriptomics data showing that progenitors are exiting the hybrid state during development.

Oscillatory Co-expression of HES1 and HES5 Enables a Hybrid State in a Bistable Transcription Factor Regulatory Motif https://www.biorxiv.org/content/10.1101/2025.05.22.655498v1

In our latest study by @veronicabiga.bsky.social, we explore how the “Oscillatory Co-expression of HES1 and HES5 Enables a Hybrid State in a Bistable Transcription Factor Regulatory Motif”:
www.biorxiv.org/content/10.1...