From preprint to publication: María Mariner spotlights ZIC2 dynamics during neural induction

A recent Short produced by preLighter María Mariner- Faulí highlights her recently published work in Nucleic Acids Research exploring how the transcription factor ZIC2 orchestrates neural cell fate during early development.

Her research uncovers a striking dual role for ZIC2: first priming chromatin accessibility, then later acting as a precise enhancer activator to drive the emergence of distinct neural identities. By integrating bulk and single-cell datasets across developmental time, the study elegantly captures how timing and regulation converge to shape the nervous system.

Originally shared as a preprint, this study went through the kind of research journey that preLights was built to follow – now coming full circle with a preLighter at the helm.

Watch the Short to hear María walk through the science and the journey behind it:

Curious to dive deeper? The full paper is now available in Nucleic Acids Research: https://academic.oup.com/nar/article/54/8/gkag374/8662368

Transcript:

During development, timing is also essential. My name is María Mariner and I have spent the last 6 years uncovering how the transcription factor ZIC2 dynamically regulates cell fate during early neural induction.

In our recently published work in Nucleic Acids Research, we show how ZIC2 plays a dual regulatory role during neural induction. It first acts as a chromatin priming factor increasing accessibility a bit everywhere. To then, as neural differentiation progresses, become a specific enhancer activator driving the expression of master regulators defining identities such as midbrain or roof plate.

While developing the project, it was incredibly insightful to see all our datasets converge. ZIC2 conditional degradation experiments helped us validate and identify ZIC2 direct targets. And it was the integration with the different bulk and single cell genomic datasets, together with the enhancer deletions, that finally helped us identify exactly which were the enhancers controlled by ZIC2 to hardwire neural progenitor identities.

And the truth is, dissecting the function of developmental transcription factors with multiple and stage specific roles is a major hurdle. So we approached this challenge by integrating our bulk and single cell datasets at sequential neural differentiation time points. This, in a way, allowed us to account for cellular heterogeneity while understanding ZIC2 function as a chromatin regulator and as a transcriptional activator at sequential neural differentiation time points.

If you’re curious to know more, the full article is currently available on Nucleic Acids Research. At the Rada-Iglesias Lab, this fantastic group of former and present lab members, we keep exploring enhancer biology from different perspectives ranging from sequence composition to transcription factor dynamics. Our goal is to solve fundamental research questions and connect the findings to congenital disease.

Before becoming a fully peer-reviewed story, this work was a preprint. A preprint which could have been highlighted as a preLight. I am a proud preLighter. preLights is a preprint highlight service run by The Company of Biologists. So if you like this way of disseminating science, do not hesitate and join the preLights community. Bye!