We suggest that increased activity of the Neanderthal EC1.45 regulatory element may have impacted SOX9 expression during development to shape lower jaw morphology.

More details in the paper - including overexpression of SOX9 in EC1.45-active cells and single cell RNA-seq to define key cell types.

We observed that the Neanderthal EC1.45 enhancer was more active than the human enhancer in a region of the developing face adjacent to the forming lower jaw.

To explore this question, we turned to recent human evolution and single nucleotide changes in EC1.45 which are found uniquely in the Neanderthal genome. From looking at the fossil record, Neanderthal jaws were very distinct to our own. Could changes in EC1.45 perhaps contribute to this difference?

One of these enhancers (EC1.45) lies a huge 1.45 megabases upstream of the SOX9 gene, yet is crucial for its expression during facial formation. We reasoned that smaller genetic changes within EC1.45 may tweak its activity and cause more subtle impacts to facial shape.

In our previous work, we explored how chromosomal translocations and large deletions upstream of the SOX9 gene may impact facial development in patients with Pierre Robin sequence (PRS). We identified two candidate enhancers active in facial progenitor cells.

doi.org/10.1016/j.stem.2020.09.001

📣 Paper alert!

I am delighted that our paper exploring the impact of Neanderthal-derived variants on the activity of a disease-associated craniofacial enhancer has been published in Development today!
journals.biologists.com/dev/article/...

And many congratulations to @eliasfriman.bsky.social and @hannahjuellig.bsky.social for their poster prizes!

The #EMBOenhanceropathies workshop was truly outstanding - such a wonderful community to be part of and exciting science from start to finish! Group photo in front of Hindsgavl Slot @edinburgh-uni.bsky.social @uoe-igc.bsky.social - we had a blast! 🧬

I had a wonderful time visiting the FMI @fmiscience.bsky.social yesterday - many thanks to @phlya.bsky.social for the kind invitation! It was great to connect with @lucagiorgetti.bsky.social, many lab members, and others across the institute. Life and science both look really fantastic in Basel!

Last week Ewa Ozga and Kasia Milto attended the Gordon Research Conference – Neural Crest & Cranial Placodes 2025!

🎤 Kasia gave a GRS talk on craniofacial disease modelling and Ewa spoke in the GRC about an adapted neural crest differentiation protocol 👩‍🏫

Beautiful venue and exciting science!

Congratulations to our poster and talk prize winners from the #hiddencelldarkgenome conference! Tiasha Ghosh, Hannah Jüllig and Hannah Wapenaar. Hannah J was presenting how Neanderthal variants impact activity of a human disease-associated enhancer - preprint here: www.biorxiv.org/content/10.1... 🧬🔬

So many proud PI moments over the last couple of weeks! @kirstyuttley.bsky.social talking about her exploration of 3D locus conformation and structural elements at the SOX9 locus at the #hiddencelldarkgenome conference. And flash talks from Hannah Juellig and Kasia Milto!

With many thanks to our keynote speakers - Emily Wong @em6wong.bsky.social, Manuel Irimia @mirimiam.bsky.social, Sean Munro, Sarah Teichmann, Wolfgang Baumeister and Christine Cucinotta @chrstne.bsky.social - what a fantastic couple of days of cross-cutting science, and a lively discussion session!

Join us for a public lecture by Dr @katarney.bsky.social!

'Enter the Dark Genome' - 2nd April, 6pm at the Royal College of Physicians of Edinburgh

Take a trip to the frontiers of biology to explore the weird and wonderful world inside your DNA...

institute-genetics-cancer.ed.ac.uk/news-events/...

There are still slots available for poster and oral presentations. Join the fantastic list of speakers:

• Emily Wong
• Manuel Irimia
• Sean Munro
• Sarah Teichmann
• Christine Cucinotta
• Wolfgang Baumeister

Conference dinner, panel discussion and a networking event all included.

See you there!

The meeting will focus on genome-wide association studies, aiming to uncover genetic foundations of facial variation. We hope the meeting will foster international and interdisciplinary collaborations and discussions. We especially encourage young and early-career researchers to submit abstracts! 🎤

Reminder of an exciting conference 'Hidden Cell, Dark Genome', Edinburgh 3-4th April 2025!

Sessions:
• Regulatory functions of the dark genome
• Uncharted proteins and RNA complexity
• Cellular diversity
• Atomic structures at the cellular scale

Early bird and registration deadline: 28th February!