Nori Zolboot

Rooted in regulation: MicroRNAs as gardeners of the Purkinje cell dendritic arbor Zolboot et al.1 developed tools to manipulate and map microRNA function in cerebellar Purkinje cells with temporal precision, revealing key roles in dendritic development and circuit connectivity. The...

How fitting that the Preview of our Neuron paper was written by the one and only Roy Sillitoe. I saw him giving a talk at the 2018 Neural Development GRC, and his incredible data, storytelling, and enthusiasm convinced me to use Purkinje Cells as a model system.
www.cell.com/neuron/fullt...

😂 both versions can be equally accurate.

Nobel laureate: I owe America my success. Today, its scientific future is in danger | CNN Dr. Ardem Patapoutian says he watches “with deep sadness as the United States’ remarkable scientific enterprise, which took generations of hard work and national investment to build, faces a concerted...

Published an op-ed for @cnn.com: “Nobel laureate: I owe America my success. Today, its scientific future is in danger.”
A personal reflection on what’s at stake as science funding gets slashed. I’d be grateful if you could amplify both in and beyond the science world.
www.cnn.com/2025/04/09/h...

How microRNAs act as a “blueprint” for the developing brain

The Lipp Lab (@lippilab.bsky.social) has uncovered how microRNAs guide the development of Purkinje cells—rare neurons tied to movement and autism.

Published in Neuron, a @cellpress.bsky.social journal, the study maps how precise timing and gene regulation shape these cells’ identity and structure.

MicroRNA mechanisms instructing Purkinje cell specification Zolboot et al. introduce DD-T6B and SAP-seq, methods for investigating microRNA function with enhanced spatiotemporal resolution, and identify Purkinje cell-specific microRNAs and targets instructing its unique dendritic arborization and climbing fiber synaptogenesis. Their findings highlight the critical role of post-transcriptional regulatory mechanisms and demonstrate the broad applicability of their tools.

Online now:

If anyone is unable to fully access the paper with the link above, please use this one: authors.elsevier.com/c/1ksln3BtfH...

a cat sitting on its hind legs with the words thank you written below it ALT: a cat sitting on its hind legs with the words thank you written below it

And of course, a HUGE thank you to the whole team who made this possible! Special shoutout to Yao (co-first author & SAP-seq god), Jess (bioinformatics guru), Marwan (Lippi lab mouse whisperer) and our fearless visionary leaders Ian and Giordano.

We greatly appreciate the support provided by the DNC vivarium staff, the core services at @scripps.edu, and @eclipsebio.bsky.social! Thank you to our editor and reviewers for their constructive feedback and a smooth, collaborative review process that helped strengthen the paper.

We think that our findings are just the tip of the iceberg, and we hope that DD-T6B, SAP-seq and our approach of dissecting miRNA-target networks can contribute to future miRNA research! Also, many exciting projects brewing in the lab on development, neural plasticity and aging. 👀

Importantly, studying miRNA-target networks in developing PCs is highly relevant for understanding neurodevelopmental disorders, such as autism spectrum disorder, where PCs are particularly vulnerable. Thank you to @autismspeaks.org for supporting this project!

Our findings suggest that adding cell type-specific layers of post-transcriptional regulation on shared transcriptomes can give rise to distinct structural features. Notably, it seems that the PC miRNA-target network acts as a brake on programs that limit dendritogenesis.

Finally, we investigated select targets that were more regulated by miRNAs in PCs compared to PNs. Strikingly, we found that repression of Prag1, Vash1, Shank3 and En2 is critical for PC dendritic and CF synaptic development.

We then compared the miRNA-target networks of PCs vs pyramidal neurons (PNs) and found subsets of targets similarly expressed in both but differentially targeted by miRNAs in PCs or PNs, hinting at transcription-independent post-transcriptional programs instructing development.

Intriguingly, we found the PC-specific miR-206 to be necessary and sufficient for elaborate dendritic arborization, a characteristic feature of PCs . We also found roles for miR-206 and miR-133 in CF synaptogenesis!

Yao and Ian developed a new method SAP-seq, which allowed us to map miRNA-target networks in rare cells like PCs for the first time! 🤯 With maps from developing PCs, we asked how PC-specific miRNAs and targets might instruct its unique dendritic arborization and CF synapses.

To get into the underlying mechanisms, we started a great collaboration with Ian MacRae’s lab at Scripps. We developed and characterized a conditional SpyTag3-AGO2 knock-in mouse line that is minimally disruptive to AGO2 function.

Curious about the “when” of miRNA function, we developed an inducible and reversible version (DD-T6B), which allowed us to identify critical windows of miRNA regulation for PC dendritic vs CF synapses (without the confounding factor of cell death caused by extended miRNA loss)

So, we repurposed the peptide T6B (from the Meister lab) for neurons to induce fast miRNA loss of function and found that contrary to prior KO studies, miRNAs are critical for PC dendritic development and climbing fiber (CF) synapse formation. (See the paper for in-depth characterization of T6B)

During my PhD, I became fascinated with Purkinje cell (PC) dendritic trees and wanted to understand if/how miRNAs were regulating its growth. Digging through the literature we realized that existing tools for miRNAs were just not sensitive enough to access PC development. 🤔

MicroRNA mechanisms instructing Purkinje cell specification Zolboot et al. introduce DD-T6B and SAP-seq, methods for investigating microRNA function with enhanced spatiotemporal resolution, and identify Purkinje cell-specific microRNAs and targets instructing ...

✨So happy to see part of my PhD work with @lippilab.bsky.social out today in @cp-neuron.bsky.social! ✨

We developed new tools to study microRNA-target networks with greater spatial and temporal resolution and found neuronal subtype- and developmental stage-specific roles:

How does gene regulation shape brain evolution? Our new preprint dives into this question in the context of mammalian cerebellum development! rb.gy/dbcxjz
Led by @ioansarr.bsky.social, @marisepp.bsky.social and @tyamadat.bsky.social, in collaboration with @steinaerts.bsky.social

Stepwise molecular specification of excitatory synapse diversity onto cerebellar Purkinje cells - Nature Neuroscience Brain function requires the formation of diverse and specific synapses. The authors show that the molecular code specifying excitatory connectivity on Purkinje cells evolves in an input-specific manne...

Stepwise molecular specification of excitatory synapse diversity onto cerebellar Purkinje cells

www.nature.com/articles/s41...

Purkinje cell sparsely labeled with GFP

Using my first post as an excuse to share one of my favorite images of a sparsely labeled Purkinje cell. I have the fortune of studying these beautiful neurons - specifically how microRNAs contribute to their remarkable dendritic arborization.

🧠🔬👩🏻‍🔬

#cerebellum #neurons #purkinjecell

Hello, I’m a postdoc at Scripps Research in San Diego and a fan of your night science podcast. This sounds exciting! I would love to learn more about your events and what you are envisioning for Postdoc Night Science and potentially help kick it off here in SD!