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

Adrian Danescu,Katherine Fu,Jaspreet Rehki,Leah Edelstein-Keshet,Johnathan Woo,Takashi Akazawa,Joy M Richman,Elisabeth G Rens

doi:10.1242/dev.193755

Adrian Danescu, Katherine Fu + Show 6 more

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https://doi.org/10.1242/dev.193755

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Abstract

ABSTRACTIn 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 of chick embryos. 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 Rho GTPase 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 asymmetrical malformations, such as non-syndromic cleft lip.This article has an associated ‘The people behind the papers’ interview.

Highlights

Facial morphogenesis requires successful passage through multiple delicate steps that must be perfectly orchestrated to give rise to the bilaterally symmetrical adult form
We demonstrate that disruption of the actomyosin network causes a loss of temporal fluctuations, causing a loss of symmetry and uncoordinated cell movements
We began by characterizing the key shape changes during frontonasal mass morphogenesis for liveimaging experiments

Summary

Introduction

Facial morphogenesis requires successful passage through multiple delicate steps that must be perfectly orchestrated to give rise to the bilaterally symmetrical adult form. More significant disturbances will lead to congenital malformations, L.E.-K., 0000-0002-2233-690X; J.M.R., 0000-0002-1409-8163. Handling Editor: Paul François Received 12 June 2020; Accepted 5 March 2021 such as cleft lip with or without cleft palate, the most common craniofacial abnormality in humans (Beames and Lipinski, 2020). The etiology of NSCLP is multifactorial, involving additive effects of multiple gene variants and interplay with environmental factors. The evidence from large studies on facial clefting shows that gene variants contribute to only 30% of the risk of NSCLP, the rest being the result of environmental stresses (Ludwig et al, 2017). The key role of environment is further highlighted by the disconcordance for cleft lip in 50-60% of monozygotic twin pairs (Grosen et al, 2011; Leslie et al, 2017)

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