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Congratulations to Yu Ji and our co-authors! This work would not have been possible without Yu's combination of computational expertise and deep functional knowledge of craniofacial and limb development.

We believe our results provide the context to understand how multiple HARs and other human-specific genetic changes acted in concert to modify defined developmental pathways, thereby driving uniquely human morphology.

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HACNS1 likely drives these changes by altering expression of its target gene Gbx2, a transcription factor, resulting in downstream effects on the regulatory networks through which Gbx2 functions.

However, we found that pre-cartilaginous domains expressing SOX9, a master regulator of chondrogenesis, were more diffuse in the pharyngeal arches compared to our control lines, suggesting delayed development. In contrast, SOX9 domains were expanded in the limb, suggesting acceleration.

We initially inferred these heterochronic shifts by comparing developmental trajectories we inferred from longitudinal single-nuclear gene expression data between the HACNS1 humanized mouse model and a model with the chimpanzee ortholog.

However, in the limb, it had the opposite effect. It accelerated chondrogenesis and drove earlier expression of differentiation-associated genes.

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Many HARs encode transcriptional enhancers with human-specific functions. We found that a single HAR, HACNS1, had opposite effects in the developing face and limb. In the face, it delayed chondrocyte development and the expression of genes involved in cartilage and skeletal maturation.

Heterochrony refers to differences in the timing of developmental events across species, e.g. humans take much longer to develop than mice even though many fundamental genetic pathways are conserved between both species

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New preprint from the lab! Using a humanized mouse model, we found that a Human Accelerated Region drives heterochronic changes in craniofacial and limb development (apologies for the re-post, we needed to adjust the thread a bit): www.biorxiv.org/content/10.6...

biorxiv.org

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Congratulations to our lead author, Yu Ji, who combined powerful computational approaches with his deep knowledge of craniofacial and limb development to make this paper possible!

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We believe our findings provide the means to understand how multiple HARs and other human-specific genetic changes may operate in defined developmental pathways to drive human-specific morphological traits.

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These shifts are likely due to HACNS1-driven changes in the expression of its target gene Gbx2, a transcription factor, and resulting changes in the regulatory networks through with Gbx2 functions.

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However, in the limb, it had the opposite effect. It accelerated chondrogenesis and drove earlier expression of differentiation-associated genes.

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We found that a single HAR, HACNS1, had opposite effects in the developing face and limb. In the face, it delayed chondrocyte development and the expression of genes involved in cartilage and skeletal maturation.

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Noonan Lab @noonanlab.bsky.social · 18/08/2026

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Congratulations to Dr. Matheo Morales for defending his thesis today! His work focused on using directed organoid models to identify differences between human and chimpanzee thalamic development.

Our newly-minted PhD graduate Matheo Morales holding a sign correctly referring to him as "Dr. Thalamus King"

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Claudia Mimoso @camimoso.bsky.social · 09/07/2026

📢 Attention Recent Graduates 📢 I’m hiring a Postgraduate Research Associate to join my growing team at Yale! If you’re passionate about RNA biology/Gene Regulation and are looking to gain hand-on research experience before graduate school, please consider applying! postdocs.yale.edu/posts/2026-0...

postdocs.yale.edu

Postgraduate Associate – RNA Biology, Genomics, Neurodevelopment - Department of Genetics, Yale School of Medicine

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Mark Peifer (He, him) @peiferlabunc.bsky.social · 02/06/2026

There is a straightforward mechanism for the public to comment. Former NIH program office Elizabeth Ginexi has written an exceptionally helpful guide on how to so, with detailed suggestions. 3/n elizabethginexi.substack.com/p/what-we-ne...

elizabethginexi.substack.com

What We Need to do NEXT: OMB’s Proposed Federal Financial Assistance Rule (OMB-2026-0034)

What OMB’s Proposed Federal Financial Assistance Rule Means in Practice

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Jeffrey Ross-Ibarra @jrossibarra.bsky.social · 29/05/2026

So no publication fees, no conferences, no international collab, and we can terminate or reject your grant anytime for any reason. This might have some impact on how science works, folks. And maybe just maybe not a positive one.

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Derek Lowe @dereklowe.bsky.social · 28/05/2026

An unapologetically angry post about what’s being done to US science:

science.org

The Current Crisis: What's Happening to Science in America

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Stand Up for Science! @standupforscience.net · 28/05/2026

BREAKING: New proposed OMB regulation, applying to all federal grants, requiring grant reviews by senior political appointees and re-emphasizes that "peer review remains advisory and does not replace agency discretion". #standupforscience public-inspection.federalregister.gov/2026-10817.pdf

public-inspection.federalregister.gov

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Alex Ip 葉清霖 @alexip718.com · 02/04/2026

One thing that amazes me is that two of the three American astronauts on board Artemis II graduated from public universities: Christina Koch earned three degrees from NC State, and Victor Glover was a defensive back on the Cal Poly football team. We are not going anywhere without public education.

youtube.com

NASA's Artemis II Crew Launches To The Moon (Official Broadcast)

YouTube video by NASA

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Bruce Hamilton @bahome.bsky.social · 28/02/2026

Very sad news. David Botstein made enormous contributions to molecular biology & genetics. I first met him in a grad school interview. I learned something from him each of the few times I saw him since. Indelible personality. Here he is giving a keynote at the 2015 UCSD Genetics Retreat.

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Gavin Sherlock @gsherloc.bsky.social · 28/02/2026

I was sad to learn that my postdoctoral mentor, David Botstein, died yesterday. I started with David as a postdoc in 1998, and he had a profound effect on both my life and scientific career. He was a giant in the field of genetics, making seminal contributions in both yeast and human genetics. 1/

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Mark Histed @markhisted.org · 20/01/2026

NIH budget bill out today. It’s the result of heavy negotiations in Congress over past month+. 🧪 Big pic: NIH budget now is abt more than funding. It’s abt restraining the technical ways NIH is being broken by Proj 2025. And the restraints in the bill are tepid 🤷‍♂️ Also: watch ICE/DHS budget. 🧵1/

United States Senate Committee on
APPROPRIATIONS
= MENU
Search
01.20.26
Committee Releases Conferenced Defense, Homeland Security, Labor, Health and Human Services, Education,
and Daldad Aaaaains and

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Dave Levitan @davelevitan.bsky.social · 03/01/2026

Cancer research costs too much but we have the money to run Venezuela

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Noonan Lab @noonanlab.bsky.social · 12/12/2025

We're truly in the darkest timeline. bsky.app/profile/timb...

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Dr. Lucky Tran @luckytran.com · 19/11/2025

I really hate it when scientists keep saying that “we need to rebuild trust in science,” because it implies that scientists are to blame for the mistrust rather than the millions of dollars of dark money that have funded political attacks on science in order to advance a far right agenda.

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We didn't investigate behavioral phenotypes in our model. However our collaborator Rebecca Muhle is studying that question so keep an eye out for results from her group.

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Thanks to the SFARI, @simonsfoundation.org, NOMIS Foundation, NICHD, NIGMS, NIMH, Charles H Hood Foundation, and NSF for supporting this work and making this paper possible!

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Thanks to @krishnaswamylab.bsky.social and David van Dijk (@vandijklab.bsky.social), who developed a core method in the paper, PHATE, and helped with data analysis in the early phases of the project.

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Congratulations to lead authors Kristi Yim, Marybeth Baumgartner (@baumoflife.bsky.social), and Martina Krenzer, in addition to co-authors María Rosales Larios, Mina Hill-Terán, Tim Nottoli, and @rebeccamuhle.bsky.social for their impressive work and perseverance on this project!

These findings suggest that CHD8 loss of function impacts gene regulatory networks and neurogenic potential of early radial glia, with distinct impacts on synaptic development and synaptic signaling of maturing excitatory neurons later in cortical development.

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Across excitatory neuron subtypes of the maturing cortex, we detected dysregulation of synaptogenesis, synaptic organization, and synaptic signaling genes, indicative of synaptic immaturity or synaptogenic delay due to CHD8 loss of function.

In radial glia of the early embryonic cortex, genes associated with risk for neurodevelopmental disorders and genes involved in chromatin remodeling, neuron projection development, and migration were downregulated.

CHD8 loss of function had cell-type-biased impacts in the developing mouse cortex, which were dynamic across development. There were distinct signatures in early radial glia, the primary progenitor cell type of the cortex, and in maturing excitatory neurons.

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We found that Chd8 and other ASD risk-associated genes had convergent expression patterns that were conserved between the mouse and human developing cortex, with expression peaking in differentiating neurons.

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We developed a mouse model of CHD8 loss of function and performed the first published single-cell transcriptomics analysis of the impacts of CHD8 loss of function across mouse cortical development.

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