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Felix Kyere (@drkyere.bsky.social)

This was a huge team effort led by myself, Felix Kyere (drkyere.bsky.social), and Ziquan Wei (ziquanw.bsky.social) under the supervision of Drs. Jason Stein (steinlab.bsky.social), Guorong Wu, and Mark Zylka. Many thanks to all our collaborators and people who have helped us through the years!

drkyere.bsky.social

PhD Candidate in http://steinlab.org studying how brain structure changes create risks for Autism. Interests: Neuroscience, Imaging and Image analysis, Data Science, Project Management, Business Strat...

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10/10 To summarize, Chd8 haploinsufficiency is a “double hit”. 💥💥In our mouse model, we find embryonic migration errors (MLH) followed by postnatal glial explosion (macrocephaly). A step forward in mapping the neuroanatomical landscape of autism! 🧩

9/10 There is a human connection to these findings. Similar heterotopias are found in post-mortem brains of people with autism, but they are rarely caught on clinical MRI due to low resolution and small size. Our study suggests we might be missing key structural abnormalities in patients!

8/10 Are these misplaced neurons just hanging out doing nothing? No! They are wired into the wider cortical circuits! 🔌 These ectopic clusters are connected via dense, aberrant myelinated tracts to the rest of the cortex!

7/10 How does the breach happen? ⚒️ Evidence suggests Chd8 loss weakens the structural barrier, by disrupting genes involved in radial glial endfoot adhesion, allowing neurons to then over-migrate where they don’t belong.

6/10 These MLH have a different timeline to the macrocephaly phenotype. They form embryonically (detected by E18.5) and stay for life. They are heavily clustered in the frontal cortex, a region critical for social cognition and executive function. 🗣️👤

5/10 But there’s a second finding! Molecular Layer Heterotopias (MLH)! These are “mushroom”-shaped cell clumps 🍄 where neurons break through the brain’s outer “fence” (the pial surface) past Layer 1.

4/10 What is driving the overgrowth? 🚙 Surprisingly, it is NOT the neurons. The growth is from the postnatal expansion of non-neuronal cells: Oligodendrocytes Microglia Glial overproduction, not neurogenesis, is the primary driver.

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3/10 Timing is everything 🕐. While macrocephaly (large brain size) is a hallmark of CHD8 syndrome, it isn’t there at birth. In this Chd8ᵛ⁹⁸⁶*ᐟ⁺ model, brain overgrowth actually emerges postnatally between P4 and P14.

2/10 We used a high-throughput multi-modal approach: Ex vivo MRI to track volume changes. 📈 Tissue clearing to make the brains transparent. 🧽 Light-sheet microscopy to count every single nucleus in 3D. 🧮 It’s a whole brain view at cellular resolution at three time-points: E18.5, P4 and P14.