🚨Reposts appreciated‼️If I had read this PhD offer five years ago, I wouldn’t have hesitated for a second to apply 😉
Passionate about gene regulation, chromatin, and developmental biology? Just contact @radaiglesiaslab.bsky.social at @ibbtec.bsky.social 🧬✨

#PhD #3DGenome

By combining the ZIC2 degron, scMultiome and additional genomic data we stringently defined the ZIC2-dependent Gene Regulatory Network (GRN) during neural induction. We showed that the genes part of this GRN are particularly sensitive to ZIC2 dosage and, thus, might be implicated in HPE etiology.

🤨Are we sure? What happens without ZIC2?
Brain patterning genes don’t turn on properly
➡️WNT signaling drops
➡️Neural progenitors skew toward more ventral fates
➡️Some even begin differentiating into neurons too early

ZIC2 doesn’t act randomly — it targets enhancers linked to patterning genes like:
➡️En1, Lmx1a/b, Pax2: playing crucial roles in midbrain and roof plate development.
➡️Wnt1, Wnt3a: core components of the WNT signaling pathway.

🎭 Act I: The Pioneer
At day 3 of differentiation (primed pluripotency), ZIC2 binds previously closed chromatin regions.
It opens them up — broadly “priming” putative regulatory elements, some linked to key neurodevelopmental genes.
📖A textbook case of pioneer transcription factor behavior.

The answer: ZIC3 steps in 💥
It is the most highly expressed ZIC family member in mESCs, and it adopts the starring role.
When we delete Zic3, pluripotency falls apart.
🧫 ZIC3 = the real main character (at this stage).

🔎This story starts with a mystery:
ZIC2 binds thousands of enhancers and promoters in pluripotent stem cells…
but when we knock it out, nothing happens. 🤷‍♀️
Cells look fine, gene expression is stable — no chaos.
🤯Why⁉️

To tackle this, we combined:
🧬CRISPR-Cas9 genome editing — to generate Zic2⁻/⁻, Zic2⁺/⁻, Zic2-FLAG-HA, and ZIC2-degron mESC lines.
📊Bulk (RNA-seq, ATAC-seq, ChIP-seq) and single-cell (Multiome RNA + ATAC) profiling — at key stages of neural differentiation.
Now, let the plot unfold...

🗨️Let me set the stage🎭: ZIC2 is essential for brain development 🧠
Mutations in ZIC2 cause holoprosencephaly (HPE), one of the most common congenital brain malformations, where the brain fails to split into two hemispheres.
But what does ZIC2 actually do at the molecular level?🕵️

Just visited the pond where my passion for developmental biology began🥹. No tadpoles in sight, but I did spot these handsome little guys. Counted over 30 frogs 🐸—most of them covered in moist soil, undergoing estivation!🥵🌄

#EMBLChromatin keeps being awesome: fantastic talks, lots of networking and troubleshooting! But guess who is also multitasking? ZIC2! Particularly during neural induction! Come by this afternoon to check poster 158 and I’ll tell you all about it 😉 @radaiglesiaslab.bsky.social

🔬💜 #11F, what a day! 💜🔬
Yesterday we brought science to the classroom.
As we left, 3 girls said they wanted to become scientists👩‍🔬. For you and for all those who will come after you: we’ll keep fighting to make sure you get there!
#WomenAndGirlsInScience