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Developmental biology - Face

Understanding Facial Formation

Research brings scientists one step closer to understanding craniofacial formation in the embryo...

In the embryo, it was known neural crest stem cells form facial features. But a new University College London (UCL) study reveals the unexpected movement of cells from the back of the head to the front to populate the face.

The new study, published in Science, reveals a surprising direction of movement likely to be very important in treating the invasion by cancer cells during metastasis, or even in subsequent facial wound healing. It may also pave the way to new therapies and treatments.
"Our findings solve a long-standing question in the scientific community about how cells move. The traditional explanation compares the process to how a train moves: an engine at the front of the train generates the force to pull the rest of the train forward. Our surprising discovery shows the engine moving the cells is at the back and not at the front."

Roberto Mayor PhD, Professor, Cell & Developmental Biology, University College London, and lead author.

This has important consequences for any new therapy based on modifying cell movement to repair facial malformation, treat facial injury, or inhibit cancer metastasis. Clinicians should consider targeting cells both at the back of the skull and in the face.

Mayor: "In the womb, neural crest cells need to migrate from the back to the front of the head in order to form the face. For the first time, we've identified how that migration happens, and it appears to be similar to how you would squeeze toothpaste from the back of a tube to move its contents to the front."

The discovery has important implications for understanding the causes of facial defects, such as cleft palate and facial palsy, which account for a third of all birth defects globally (3.2 million each year) and are the primary cause of infant mortality.

For the study, researchers worked with both frog and fish embryos, as their neural crest cells behave in a similar way to those of humans. As patterns of cell movement are often used to approach the spread of facial cancers, Mayor's team used a technique called optogenetics to follow the behavior of clusters of neural crest cells. After identifying that a protein 'cable' acctually surrounds these cell clusters, scientists watched as the 'cable' contracted. Illuminated with the laser beam, they saw neural crest cells at the back of the embryo head process squeeze neural crest cells forwards into the facial area.
"By clarifying how faces develop, we can begin to investigate how that process can occur incompletely or differently to cause facial defects, and hopefully identify ways to prevent such harmful defects."

Adam Shellard PhD, Department of Cell and Developmental Biology, University College London, London, UK. and a co-author on the paper.

Collective cell chemotaxis, the directed migration of cell groups along gradients of soluble chemical cues, underlies various developmental and pathological processes. We use neural crest cells, a migratory embryonic stem cell population whose behavior has been likened to malignant invasion, to study collective chemotaxis in vivo. Studying Xenopus and zebrafish, we have shown that the neural crest exhibits a tensile actomyosin ring at the edge of the migratory cell group that contracts in a supracellular fashion. This contractility is polarized during collective cell chemotaxis: It is inhibited at the front but persists at the rear of the cell cluster. The differential contractility drives directed collective cell migration ex vivo and in vivo through the intercalation of rear cells. Thus, in neural crest cells, collective chemotaxis works by rear-wheel drive.

Adam Shellard, András Szabó, Xavier Trepat, Roberto Mayor.

The study was conducted by researchers at UCL and the Barcelona Institute of Science and Technology, and was funded by the Medical Research Council, Biotechnology and Biological Sciences Research Council and Wellcome.

Published by the American Association for the Advancement of Science

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Oct 24, 2018   Fetal Timeline   Maternal Timeline   News   News Archive

Neural crest cells migrate throughout an embryo as it develops. Shellard et al. used frog and zebrafish embryos to study how clumps of mesenchymal cells migrate. Mesenchymal cells are connective tissue cells and will not become blood cells. These cells move powered by a actomyosin cable that contracts around the rear of that clump of cells. Similar supracellular contractability at the front of this clump of cells is inhibited by chemical signals. The imbalance in these two forces causes cells to rearrange so that the whole clump can be propelled forward. Credit: Science, this issue p. 339; see also p. 290

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