In vivo DNA damage protection during cell migration across confining embryonic tissue environments

Nuclear morphometrics analysis shows that neural crest experience dramatic nuclear deformation during their migration between adjacent tissues, which quantitatively scales with tissue confinement. By using complementary genetic and mechanical strategies to ablate the surrounding tissue, we observe a rescue of nuclear deformation in vivo. Surprisingly, we found that while deformation of the neural crest nucleus causes nucleo-cytoplasmic leakage, it does not cause nuclear envelope rupture or increase DNA damage even upon extreme deformations.

Instead, confined migratory neural crest show decreased LaminB2 at the nuclear envelope. By perturbing LaminB2 expression levels, we discover that loss of LaminB2 facilitates fast recovery from deformation, while sustained expression of LaminB2 results in persistently deformed nuclei, highlighting a role for LaminB2 in nuclear shape deformability. Using a photoconversion and RNA-seq approach, we uncover upregulation of a large network of DNA repair genes in confined trunk neural crest, suggesting these stem cells might be resistant to confinement-induced mechanical stresses.

In summary, we establish the neural crest as a physiological framework, uncovering dynamic adaptations to tissue confinement in vivo.