Eric Brooks

In December's #EditorsChoice, Nayeli Reyes-Nava, @edwardmarcotte.bsky.social, @jbwallingford.bsky.social & co use #Xenopus model to study #Cilia motility disturbances in primary ciliary dyskinesia #PCD

⚡ doi.org/10.1242/dmm....
📰 doi.org/10.1242/dmm....

Genetically engineered ESC-derived embryos reveal Vinculin-dependent force responses required for mammalian neural tube closure https://www.biorxiv.org/content/10.64898/2025.12.22.696028v1

This was such a fun project where we uncovered many fascinating details, including a surprising regulatory layer to Hh signaling acting along the AP axis to influence both cell fates and the apical constriction program driving closure. Really grateful to Sun-Hee, Saikat and Kevin!

GPR161–GLI3 repressor signaling at cilia directs apical constriction and cell fate during cranial neural tube closure Highlighted Article: Cilia-dependent GLI3 repression controls patterns of cell fate and apical remodeling during cranial neural tube closure in mouse.

The final manuscript detailing a great collaborative effort between Saikat Mukhopadhyay's group and ours, spearheaded by the amazing Sun-Hee Hwang is out now! We disambiguate the roles of activating and repressive arms of Hh signaling during cranial neural tube closure. doi.org/10.1242/dev....

Floor plate marker ventralization in E9.25 Gpr161 ko forebrain is selectively rescued by Gli3R expression but not from Gli2 deletion. (A) Forebrain (top) and hindbrain (bottom) cranial horizontal sections immunostained using designated markers from embryos dissected at E9.25 (18-22 somites, except Gli2 ko/ko at 25 somites) of the following genotypes: wild-type (n=6), Gpr161ko/ko (n=3), Gli3RΔ701/+ (n=6), Gpr161ko/ko; Gli3RΔ701/+ (n=3), Gli2ko/ko (n=6), Gpr161ko/ko; Gli2ko/ko (n=6). The same sections for each genotype were co-stained for FOXA2 and NKX6-1 and consecutive sections for PAX6. All images are counterstained with DAPI. Scale bars: 100 µm. FB, forebrain; HB, hindbrain; OC, optic cup. See also Figs S2 and S3, which show magnified forebrain and hindbrain images of the same sections (except for staining of separate closed hindbrain sections for Gpr161ko/ko; Gli3RΔ701/+ and Gpr161ko/ko; Gli2ko/ko and additional staining for OLIG2 for all genotypes). Additional anterior to posterior sections in Gpr161ko/ko; Gli2ko/ko brain are shown in Fig. S2. (B,C) Quantification of FOXA2 dorsoventral (D-V) extent and ventral-most PAX6 extent with respect to full extent of the neural tube in forebrain and hindbrain regions. All data shown as mean±s.d. Note forebrain FOXA2 ventralization in Gpr161ko/ko rescued by Gli3R expression only, whereas hindbrain FOXA2 ventralization in Gpr161ko/ko is rescued by Gli3R expression or Gli2 deletion. Ventral-most PAX6 extents are not impacted from ventralized FOXA2 levels in Gpr161ko/ko; Gli2ko/ko. (D) Summary of the regionalized impacts on dorsoventral neural precursor patterning. WT, wild type.

The prickly consequences of Hedgehog de-repression on cranial neural tube closure

This Research Highlight showcases work by Eric R. Brooks @tomorrowbot.bsky.social, Sun-Hee Hwang, Kevin A. White and Saikat Mukhopadhyay:

journals.biologists.com/dev/article/...

Thanks to @devbiol.bsky.social for featuring our work! This was a great project, though one with many confusing turns at times, which only seems right for exploring something to do with such a re-iteratively used pathway as Wnt signaling

The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture - Nature Communications The CPLANE complex is essential for ciliogenesis, and mutations to all but one subunit have been associated with ciliopathies. Here they identify three familial mutations in the final subunit, RSG1, t...

Cilia Alert! So excited to finally have this paper on the CPLANE complex out in @natcomms.nature.com! We show that RSG1 is a human ciliopathy protein and links CPLANE to the transition zone. 1/n

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

A look at the developing human embryonic forebrain in 3D!

Post-doc @stochastalive.bsky.social shares this week's image showing a dorsal view of the human embryonic forebrain at Carnegie Stage 16 (~6 weeks post conception). Major regions marked by FOXG1, WNT8B, PAX6, and SHH are displayed.

Dynamic Landscape Analysis of Cell Fate Decisions: Predictive Models of Neural Development From Single-Cell Data Building a mechanistic understanding of cell fate decisions remains a fundamental goal of developmental biology, with implications for stem cell therapies, regenerative medicine and understanding dise...

Our latest "Dynamic Landscape Analysis of Cell Fate Decisions: Predictive Models of Neural Development From Single-Cell Data"

A rigorous mathematical foundation for Waddington's landscape to study cell fate decision making

Applied to ventral neural tube development

www.biorxiv.org/content/10.1...

#ApicalConstriction and #DevBio afficionados - we've got two new pre-prints you may be interested in, below:

We are doing well and it's definitely neat to have a UT reunion here many years down the road!

Congrats on the big year, Ben!

WOW! Been a crazy busy year but we've gotten a lot of stuff across the finish line. All the credit to my team here at U of L and our collabs at IU SOM, Oxford, CU Anschutz and UC Merced! Gonna update y'all with this Bluetorial!

The ciliary protein C2cd3 is required for mandibular musculoskeletal tissue patterning. Evan C. Brooks, Ph.D. Graduate Student Alumnis, Brugmann Lab, Cinicinnati Children's Hospital Medical Center. Currently: Postdoctoral Fellow, University of Colorado School of Dental Medicine. "Biological Differentiation Across the Scales" Seminar, April 28, 2025.

The "Biological Differentiation Across the Scales" virtual seminar series kicked off on April 28 with an insightful, engaging talk by @ecbrooks96.bsky.social. Missed it live? Watch the recording: www.isdifferentiation.org/Journal/Page... @rogerslabucd.bsky.social @uribelab.bsky.social #devbio

On a final note, we would like to thank our reviewers for their enthusiasm about this work and for their experimental and analytical suggestions which significantly strengthened this study.

Thus, Wnt activity levels must be modulated throughout cranial neural tube closure in order to control both proliferation and cell remodeling in order for closure to complete.

Conversely, conditional inactivation of APC and resulting hyperactivation of Wnt signaling, leads to apical constriction blockade by altering actin organization, and this occurs without changes in proliferation or tissue scaling.

Loss of robust Wnt signaling in Lrp6 mutants drives an early burst of excessive cell proliferation in the cranial tissues, leading to a doubling of the tissue volume and width. This excessive width blocks closure despite the normal function of cell remodeling programs, including apical constriction.

In this study we find that either hypomorphic or hypermorphic Wnt signaling states lead to cranial neural tube closure defects, but interestingly the underlying cellular defects in pathway activity states are distinct.

Canonical Wnt pathway modulation is required to correctly execute multiple independent cellular dynamic programs during cranial neural tube closure Defects in cranial neural tube closure are among the most common and deleterious human structural birth defects. Correct cranial closure requires the …

We are pleased to share the version of record of our study on the complex role of Wnt signaling in control of cell behavior during cranial neural tube closure. This work was spearheaded by the fantastic Amber Bogart and is out now in @devbiol.bsky.social www.sciencedirect.com/science/arti...

Canonical Wnt pathway modulation is required to correctly execute multiple independent cellular dynamic programs during cranial neural tube closure Defects in cranial neural tube closure are among the most common and deleterious human structural birth defects. Correct cranial closure requires the …

A gorgeous (first of many!) paper out of the Brooks Lab (@tomorrowbot.bsky.social): www.sciencedirect.com/science/arti...

Neural tube closure! Wnt signaling! Cell proliferation! Quantitative microscopy! What’s not to love?

Mapping brain development A new study provides a two-dimensional gene expression map during early brain development.

A new 2D gene expression map of the mouse brain during early development.

Join us for the @socdevbio.bsky.social Southeast Regional Meeting, May 19-21! www.sdbonline.org/sesdb2025 Showcase your exciting research & receive valuable feedback at any stage, from a newly fertilized idea to a rapidly gastrulating hypothesis to a fully 'developed' story. 🙂 #SESDB2025 #DevBio

A single-cell atlas of spatial and temporal gene expression in the mouse cranial neural plate Single-cell RNA sequencing and computational analysis define a spatial and temporal map of gene expression during early patterning and morphogenesis of the mouse cranial neural plate, providing a reso...

Excited to share the version of record of our study of patterned gene expression during the earliest stages of neural development, out now in @elife.bsky.social! A single-cell atlas of spatial and temporal gene expression in the mouse cranial neural plate doi.org/10.7554/eLif...

My daily haiku from grant writing:

More words fall beneath
The stoke of my delete key
Concision triumphs

Images of mouse embryos spanning the stages of cranial neural tube closure

A new single-cell atlas of gene expression provides insights into the patterning of the neural plate of mice.

🔗 https://elifesciences.org/articles/105042?utm_source=bluesky&utm_medium=social&utm_campaign=organic_insights

Together, these analyses suggest that Wnt activity levels must be strictly modulated to tune both tissue scaling and curvature change during cranial closure.

On the other hand, hyperactivation of Wnt signaling by conditional inactivation of APC specifically in the cranial folds blocks apical constriction, preventing neural fold elevation.

We find that reduced Wnt signaling in Lrp6 mutants leads to a surprising tissue hyperplasia phenotype in the cranial neural plate, which leads to a doubling of tissue width, preventing closure. This hyperplasia is driven by an early doubling of proliferation specifically in anterior cranial tissues

Wnt pathway modulation is required to correctly execute multiple independent cellular dynamic programs during cranial neural tube closure Defects in cranial neural tube closure are among the most common and deleterious human structural birth defects. Correct cranial closure requires the coordination of multiple cell dynamic programs inc...

Pleased to present the first preprint from our group, spearheaded by the fantastic Amber Bogart. We examined the consequences of either reduced or hyperactivated Want signaling on the cellular drivers of cranial closure. www.biorxiv.org/content/10.1...