by Scientists from UCL, the Wellcome Sanger Institute, the University of Oxford, and collaborators have recently uncovered the crucial function of a protein named Cachd1 in the development of brain asymmetry. This groundbreaking research, published in the journal Science, sheds light on the genetic mechanisms behind the brain’s unique left–right differences and could pave the way for a better understanding of human disorders where brain asymmetry is disrupted.
By conducting genetic screening experiments on zebrafish, researchers discovered that when Cachd1 was mutated, the right half of the brain lost its normal asymmetric development and instead mirrored the left side. This disruption led to abnormal neural wiring, potentially affecting brain function.
The findings reveal that Cachd1 plays a significant role in establishing the distinct neural wiring and functions on each side of the brain. The protein binds to two receptors that allow cells to communicate through the Wnt signaling pathway, a vital pathway for cellular communication during early development, Stem Cell formation, and many diseases.
The team also found that Cachd1’s influence appears to be specific to the right side of the brain, suggesting the presence of an unknown inhibitory factor restricting its activity in the left side. While the full details are yet to be uncovered, the evidence strongly suggests that Cachd1 plays a crucial role in establishing the differences between the left and right sides of the developing brain by regulating cellular communication specifically on the right side.
This collaborative project, which brought together researchers from genetics, biochemistry, and structural biology, has provided new insights into both Wnt signaling and the development of brain asymmetry. Future research will explore the potential other important functions of Cachd1 involving the Wnt pathway.
Dr. Gareth Powell, co-first author of the study and former Ph.D. student at the Wellcome Sanger Institute, now based at UCL Cell & Developmental Biology, expressed his excitement about the publication, stating, “I am happy to see the publication of this highly collaborative study that has brought together many talented people with varied research interests and skills from multiple institutes.”
Professor Steve Wilson, senior author of the study, at UCL Cell & Developmental Biology, also shared his enthusiasm, “Together, the team have allowed us to make exciting new insights into both Wnt signaling and the development of brain asymmetry.”
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