Symmetry and fluctuation of cell movements in neural crest-derived facial mesenchyme.

In the face, symmetry is established when bilateral streams of neural crest cells leave the neural tube at the same time, follow identical migration routes and then give rise to the facial prominences. However developmental instability exists, particularly surrounding the steps of lip fusion. The causes of instability are unknown but inability to cope with developmental fluctuations are a likely cause of congenital malformations such as non-syndromic orofacial clefts. Here, we tracked cell movements over time in the frontonasal mass which forms the facial midline and participates in lip fusion using live-cell imaging. Our mathematical examination of cell velocity vectors uncovered temporal fluctuations in several parameters including order/disorder, symmetry/asymmetry and divergence/convergence. We found that treatment with a RhoGTPase inhibitor completely disrupted the temporal fluctuations in all measures and blocked morphogenesis. Thus we discovered that genetic control of symmetry extends to mesenchymal cell movements and that these movements are of the type that could be perturbed in in asymmetrical malformations such as non-syndromic cleft lip.