Huntington’s disease is a fatal condition involving the death of brain cells, typically striking in midlife. But new findings suggest the disease process starts decades earlier. Although symptoms emerge in adulthood, researchers have been able to detect the earliest effects of Huntington’s in the first two weeks of human embryonic development.
In the new study, researchers examined the effects of Huntington’s mutation at an earlier stage, called gastrulation, during which the two-week-old embryo starts to form the three embryonic germ layers, from which the progenitors of all cell types, including brain cells emerge.
For the study, the researchers created synthetic human embryos — lab-generated embryos that are derived from stem cells and mimic the behavior of human cells during the early stages of development. They then used the gene-editing method CRISPR/Cas9 to insert the range of Huntington’s mutations found in people with the disease into the embryos.
Journal Reference: Huntingtin CAG expansion impairs germ layer patterning in synthetic human 2D gastruloids through polarity defects. Development, 2021; 148 (19) DOI: 10.1242/dev.199513