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\DOI{10.5802/crbiol.145}
\datereceived{2023-10-05}
\dateaccepted{2023-11-07}
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\begin{document}

\begin{noXML}

\RubricEF{Review Article}{Article de revue}

\title{Organizing collective cell migration through guidance by followers}

\alttitle{Organiser la migration cellulaire collective via le guidage
par les suiveuses}

\author{\firstname{Arthur} \lastname{Boutillon}\CDRorcid{0000-0002-0968-6059}}
\address{Cluster of Excellence Physics of Life, Technische
Universit\"{a}t Dresden, 01062~Dresden, Germany}
\email{arthur.boutillon@tu-dresden.de}

\begin{abstract}
Morphogenesis, wound healing, and some cancer metastases rely on the
collective migration of groups of cells. In these processes, guidance
and coordination between cells and tissues are critical. While strongly
adherent epithelial cells have to move collectively, loosely organized
mesenchymal cells can migrate as individual cells. Nevertheless, many
of them migrate collectively. This article summarizes how migratory
reactions to cell--cell contacts, also called ``contact regulation of
locomotion'' behaviors, organize mesenchymal collective cell migration.
It focuses on one recently discovered mechanism called ``guidance by
followers'', through which a cell is oriented by its immediate
followers. In the gastrulating zebrafish embryo, during embryonic axis
elongation, this phenomenon is responsible for the collective migration
of the leading tissue, the polster, and its guidance by the following
posterior axial mesoderm. Such guidance of migrating cells by followers
ensures long-range coordination of movements and developmental
robustness. Along with other ``contact regulation of locomotion''
behaviors, this mechanism contributes to organizing collective
migration of loose populations of cells.\vspace*{-2pt}
\end{abstract}

\begin{altabstract}
La morphog\'{e}n\`{e}se, la cicatrisation et certains types de
m\'{e}tastases reposent sur la migration collective de groupes de
cellules. Lors de ces processus, le guidage et la coordination entre
cellules et entre tissus sont fondamentaux. L\`{a} o\`{u} les tissus
\'{e}pith\'{e}liaux, tr\`{e}s adh\'{e}sifs, doivent se d\'{e}placer
collectivement, les cellules m\'{e}senchymateuses, en ordre l\^{a}che,
peuvent migrer individuellement. Cependant, de nombreuses cellules
m\'{e}senchymateuses migrent de mani\`{e}re collective. Cet article
r\'{e}sume comment les r\'{e}actions migratoires aux contacts entre
cellules, aussi appel\'{e}es \og{}~r\'{e}gulation de locomotion par
contact~\fg{}, organisent la migration collective des cellules
m\'{e}senchymateuses. Il d\'{e}crit en particulier un m\'{e}canisme
r\'{e}cemment d\'{e}couvert, le \og{}~guidage par les suiveuses~\fg{}, par
lequel une cellule est orient\'{e}e par les suiveuses imm\'{e}diatement
en contact. Dans l'embryon de poisson-z\`{e}bre en gastrulation, lors
de l'\'{e}longation du m\'{e}soderme axial, ce ph\'{e}nom\`{e}ne est
responsable de la migration collective du tissu au front, le polster,
et de son guidage par le tissu qui le suit, le m\'{e}soderme axial
post\'{e}rieur. Ce m\'{e}canisme de guidage par les suiveuses garantit
la coordination des mouvements sur de longues distances ainsi que la
robustesse du d\'{e}veloppement. Avec les autres processus de
\og{}~r\'{e}gulation de locomotion par contact~\fg{}, ce m\'{e}canisme
contribue \`{a} organiser la migration de groupe de cellules en ordre
l\^{a}che.
\end{altabstract}

\keywords{\kwd{Collective cell migration}
\kwd{Embryonic development}
\kwd{Mechanosensation}
\kwd{Cell polarization}
\kwd{Zebrafish}
\kwd{Mesenchymal cell}
\kwd{Mesoderm}}

\altkeywords{\kwd{Migration cellulaire collective}
\kwd{D\'{e}veloppement embryonnaire}
\kwd{M\'{e}canoperception}
\kwd{Polarisation cellulaire}
\kwd{Poisson z\`{e}bre}
\kwd{Cellule m\'{e}senchymateuse}
\kwd{M\'{e}soderme}}

\def\thanksname{Note}
\thanks{Arthur Boutillon received the Grandes Avanc\'ees en Biologie
2023 award}

\maketitle

\vspace*{-3pt plus 1pt minus 1pt}
\twocolumngrid

\end{noXML}

\section{Introduction} 

Cell migration, the active and directed movement of cells from one
location to another in response to a signal, is a fundamental and
intricate process that plays a critical role in various biological
phenomena, ranging from embryonic development and tissue repair to
immune responses and cancer metastasis. It is essential for shaping
tissues and organs during development as well as maintaining tissue
homeostasis.\looseness=-1

Some cells migrate as individual cells that navigate their environment.
However, many cells migrate collectively, as part of cell
groups~\cite{37}. The term ``collective migration'' has received
different definitions. Historically, it was first used to describe the
movement of epithelial cells which are closely adhesive to one another,
and therefore necessarily move collectively~\cite{43,60}. However,
the definition was more recently widened to all migrations in which the
movement of one cell is modulated by the other migrating cells and
where the group of cells acts as a 
cooperative unit~\cite{56}.
Experimentally, this can be 
revealed by isolating cells which are then
unable to exhibit the migratory behavior they display in the group.

In this article, we briefly review the different cellular behaviors
that ensure collective migration, in~\mbox{particular} the ``contact
regulation of locomotion'' mechanisms organizing mesenchymal cells,
with a focus on Xenopus neural crest cell migration. In a second time,
we highlight the recent discovery of ``guidance by followers'', a
behavior ensuring collective cell migration and coordination of the
movement of different tissues.

\section{Collective cell migration and contact regulation of locomotion}

During collective epithelial cell migration, the collective nature of
the movement mainly stems from the fact that cells are tightly attached
to each other. Such migration has been extensively described, in
particular using epithelial monolayers in a so-called wound healing
assay~\cite{57,60}. A gap is formed in a confluent epithelial
monolayer, usually by scratching the monolayer or by removing a
stencil, and cell movements are recorded. Although the details of the
cellular behavior vary depending on the cell type, the migration of
epithelial monolayers overall relies on the formation of leader cells
facing the empty space. These cells adopt migratory features, forming a
large lamellipodium and dragging surrounding cells in a finger-like
structure. The rest of the cells then adopt a follower morphology,
either being passively dragged or forming small, cryptic lamellipodia
contributing to local movement~\cite{40,42,60}.

Although epithelial tissues \textit{in vivo} usually display more
complex structures, their collective migration also relies on an
organization in which leaders set the movement and followers are
dragged along~\cite{13,22,31}. During zebrafish development, the
primordium of the posterior lateral line forms a small cluster of cells
migrating along a track of chemoattractant. This cluster is set in
motion by a small group of leader cells detecting a local gradient of a
chemoattractant, which is generated by the follower cells, that are
then dragged by the leading cells~\cite{15,16,17,22,61}. Separating
leaders and followers~\cite{36} or changing their
identity~\cite{10,16,22,59} largely disrupts primordium migration,
showing the need for cooperation between cells with distinct leader and
follower roles.

While mesenchymal cells are not strongly attached to their neighbors
and sometimes migrate individually~\cite{1}, some of them organize
in a migrating group. In the group, cells all display a migratory
behavior forming actin rich protrusions, adopting a loose order with
only transient contacts and often changing neighbors. Such organization
can be the \mbox{result} of the concomitant movement of cells migrating
independently from each other, for example immune cells migrating
towards the site of a wound~\cite{32}. In other instances,
cooperation between cells is actually required for proper group
migration, thus constituting a \textit{bona fide} collective cell
migration. In these cases, isolated cells behave differently than in
the group and are unable to migrate efficiently \cite{49,54}.
\looseness=-1

Given the loose nature of mesenchymal tissues, cooperative processes
leading to collective migration differ compared to epithelial tissues.
One of the most extensively described instances of mesenchymal
collective migration is that of Xenopus neural crest
cells~\cite{44,55}. These cells display a surprisingly large
diversity of migratory behaviors (durotaxis, chemotaxis, electrotaxis,
etc.)~\cite{4,5,19,46,53}, but their migration is
mainly driven by two phenomena: contact inhibition of
locomotion~\cite{11} and co-attraction~\cite{12,45}. Contact
inhibition of locomotion was described a century ago~\cite{30} and
corresponds to the tendency of two colliding cells to stop and then
reorient their movement away from the collision site 
(Figure~\ref{fig1}A)~\cite{2,50}. 
Without additional mechanisms, this would lead
to cell dispersal, as cells tend to flee contact. Co-attraction
corresponds to the expression of both a chemoattractant and its
receptor. Thus, cells attract each other, coalescing into a
cluster~\cite{12}. The combination of these two properties in the
neural crest cells generates a complex behavior where cells tend to
move away from a cluster because of contact inhibition of locomotion
while at the same time reforming a cluster thanks to co-attraction.
This leads to persistent displacement in a laterally constrained
environment~\cite{51}.\looseness=-1

\begin{figure*}
\vspace*{-3pt}
\includegraphics{fig01}
\vspace*{-3pt}
\caption{\label{fig1}Different modes of contact regulation of
locomotion. (A) Contact inhibition of locomotion corresponds to the
active repolarization of two colliding cells away from the contact
point. {(B)} Contact enhancement of locomotion is the
stabilization of cell migration direction upon contact with another
cell. {(C)} Contact following of locomotion is the alignment of
a cell contacting the posterior side of a leading cell, resulting in
the formation of a small train of cells. Cells are color-coded
according to their identity.}
\vspace*{-3pt}
\end{figure*}

Two types of contact inhibition are reported depending on what happens
after cell collision~\cite{50}. In type-I contact inhibition of
locomotion, colliding cells actively migrate away from each other,
forming migratory structures at the opposite side compared to the point
of collision. In type-II contact inhibition of locomotion, cells simply
reorient their migration after colliding with another cell, although
there is a debate about whether this is actually an active process or
simply the result of steric hindrance.

Until recently, contact inhibition of locomotion was considered to be
the main phenomenon \mbox{controlling} collective behavior and interaction
between colliding cells. However, recent studies have described two
other cellular behaviors upon cell--cell contact. In a minimalist system
where cell collision is controlled, it has been observed that when the
front of a cell collides with the rear of another cell, the rear cell
tends to stay attached to the front cell and to follow its migration
(Figure~\ref{fig1}B)~\cite{29}. This phenomenon, called ``contact
following of locomotion'', can lead to the formation of small trains of
collectively migrating cells. Such a behavior has recently been
observed in colonies of Dictyostelium Discoideum~\cite{24}. In the
same organism, it has also been described that collision between cells
tends to stabilize the migration of both cells~\cite{14}. This
phenomenon, termed ``contact enhancement of locomotion'', tends to
accelerate the spreading of colonies (Figure~\ref{fig1}C). It has
recently been proposed to group these contact-driven behaviors under
the name ``contact regulation of locomotion''~\cite{3}, to stress
that these behaviors rely on cell signaling and active cell responses,
and to distinguish them from purely physical collective phenomena such
as plithotaxis, the alignment in the direction of the lowest shear
stress~\cite{52}. These different instances show that there is a
whole repertoire of cellular responses to contact in addition to
contact inhibition of locomotion, offering a wide range of mechanisms
for coordinating collective migrations.

In a recent paper, in order to better understand how interactions
between cells coordinate migration, we studied the elongation of the
axial mesoderm of the zebrafish embryo during
gastrulation~\cite{7}. We discovered another phenomenon of contact
regulation of locomotion leading to collective migration in a
mesenchymal tissue and its coordination with other tissues. In the
anterior axial mesoderm, cells detect the active migration of cells
immediately behind them and align their migration accordingly, a
behavior we named ``guidance by followers''.

\section{A novel process underlying mesenchymal collective migration}

During gastrulation, the zebrafish embryo is made of a big spherical
yolk cell on top of which sit the embryonic cells, exhibiting three
major concomitant cellular movements: epiboly, ingression, and
convergence and extension (Figure~\ref{fig2}A--D). Epiboly consists of
a movement of the embryonic margin towards the vegetal pole of the
embryo~\cite{9,62}. Ingression is the movement of cells at the
margin towards the yolk cell to form the deep hypoblast below the
surface epiblast~\cite{33,39,38,62}. Finally, convergence
and extension corresponds to a global movement from both hypoblast and
epiblast cells of convergence towards the\break dorsal midline and of
extension along the animal-vegetal axis~\cite{62,63}.

\begin{figure*}
\vspace*{-2pt}
\includegraphics{fig02}
\vspace*{-2pt}
\caption{\label{fig2}Axial mesoderm during zebrafish gastrulation.
(A--D) Pictures of Gsc:GFP embryo, a transgenic line labelling axial
mesoderm, during gastrulation and corresponding schematics. {(A,B)}
Dorsal view. {(C,D)} Side view. {(A,C)}
Purple and white dashed lines respectively delimit polster and
posterior axial mesoderm, both labelled in green in this transgenic
line; red dashed line marks the embryonic margin. epi: epiblast; po:
polster; pm: posterior mesoderm. {(B,D)} Epiboly, convergence
and extension and ingression movements are depicted by red, grey and
purple arrows respectively. A: animal; Veg: vegetal; R: right; L: left;
D: dorsal; V: ventral. {(E,F)} Pictures of Gsc:GFP transgenic
axial mesoderm during gastrulation in side and dorsal view
respectively. Axial mesodermal cells are labelled in green and
membranes in red. Purple and white dashed lines respectively delimit
polster and posterior axial mesoderm. All scale bars are 50~${\upmu}$m
long. Adapted from~\cite{7,48}, all rights reserved.}
\vspace*{-1pt}
\end{figure*}

The axial mesoderm is a structure that elongates during gastrulation
from the dorsal margin towards the animal pole of the embryo and is
composed of two tissues (Figure~\ref{fig2}E, F). The polster, closest
to the animal pole, is a mesenchymal tissue composed of roughly
200~cells in a loose, three-dimensional
arrangement~\cite{18,28,34}. Polster cells display active
migratory behavior oriented towards the animal pole of the embryo. They
are followed by the posterior axial mesoderm, which undergoes
convergence and extension, maintaining contact with the polster during
its migration~\cite{20,28}.

Because all polster cells display similar oriented migratory behavior,
it has initially been thought that they were migrating independently
from each other~\cite{26}. However, transplantation experiments,
have shown that single cells, or small groups of cells, when isolated
from the rest of the polster, would remain motile but lose their
orientation towards the animal pole~\cite{18}. Conversely, these
isolated cells recovered their orientation upon contact with the
polster. These experiments established polster migration as a
\textit{bona fide} instance of collective cell \mbox{migration} and suggested
that the directional information that guides polster cell migration is
contained within the polster and is transmitted between cells via
cell--cell contacts by an unknown mechanism.

In order to understand the guidance of polster migration, we sought to
locate the information of direction in the tissue by removing or
isolating portions of the tissue and observing which parts are
necessary to drive migration. For this purpose, we developed spatially
confined three-dimensional laser ablations using a pulsed laser, to
ablate precisely individual polster cells in the deep hypoblast,
without affecting neighboring tissues
(Figure~\ref{fig3}A)~\cite{6}. We then performed various cuts in
the polster and first noticed that removal of the first rows of cells
does not affect polster migration, suggesting that there is no specific
leader role for these cells~\cite{41}. More importantly, we observed
that the polster, when \mbox{separated} from the posterior mesoderm, is unable
to orient its \mbox{migration} autonomously. However, when contact with the
posterior mesoderm is preserved, migration is oriented, suggesting that
interaction with the posterior mesoderm is actually required for
directionality. We confirmed this observation using microsurgery and
cell transplantations~\cite{8}. It thus appeared that, contrary to
our expectations, the directional information guiding the polster is
not self-contained in the polster, but is in fact provided by the
following tissue.

\begin{figure*}
\includegraphics{fig03}
\caption{\label{fig3}Experimental demonstration of guidance by
followers. A schematic, a representative image and simplified results
are presented for each experiment. Compasses and barred compasses
respectively indicate oriented and misoriented migration or migratory
behavior. {(A)} Deep, three dimensional and spatially restrained
laser ablations. Red lines on the microscopy image and on the small
axial mesoderm schematics indicate position of the cut, purple and
white dashed lines respectively delimit polster and posterior axial
mesoderm. {(B)} Transplantation of a WT polster in a host where
the posterior axial mesoderm is slowed. Transplanted polster cells are
labelled with red nuclei on the microscopy image. White and purple
dashed lines respectively indicate the host posterior axial mesoderm
and the transplanted polster. {(C)} Isolation of WT polster
cells from a WT axial mesoderm by migration deficient buffer cells. WT
transplanted cells, buffer cells and host are respectively labelled in
red, with blue nuclei or in plain green. Purple dashed line indicates
the front of host axial mesoderm. {(D)} Transplantation in a WT
host of perturbed polster cells overexpressing or depleted for specific
proteins.  Transplanted polster cells are labelled in red. Purple and
white dashed lines respectively delimit polster and posterior axial
mesoderm. All scale bars are 50~${\upmu}$m long. Adapted
from~\cite{7}, all rights reserved.}
\end{figure*}

We then sought to understand how interaction with the posterior
mesoderm drives polster migration. In particular, since the posterior
mesoderm elongates during gastrulation, we tested whether extension is
required for polster guidance (Figure~\ref{fig3}B). Using microsurgery
approaches and functional genetics, we specifically manipulated the
extension speed of the posterior mesoderm. It turned out that the
orientation of a wild-type polster is lost when the following posterior
mesoderm elongates more slowly. This shows that proper elongation of
the posterior tissue is required for polster guidance.

To explain how the movement of the following tissue could orient the
polster, we considered two hypotheses. Polster cells could orient
either by detecting the fact of being pushed, for example by feeling an
induced stress, or by detecting an oriented signal from the following
cells, like their active migration. Using multiple microsurgery and
cell transplantation, we isolated some polster cells from the rest of
the tissue by introducing a row of buffer cells whose migration was
perturbed, being either non-protrusive, non-oriented or non-adhesive
(Figure~\ref{fig3}C). Despite being pushed by axis extension, such
isolated cells are not oriented, showing that polster cells detect the
active, oriented migration of their neighbors and align with it.

We then dissected the molecular mechanism underlying the detection of
neighbors' migration using gene loss of function (Figure~\ref{fig3}D).
We identified that the adherens junction complex
E-Cadherin/${\upalpha}$-Catenin/Vinculin is required for polster
orientation. Interestingly, ${\upalpha}$-Catenin is a mechanosensitive
protein, able to trigger cell signaling and recruit the adapter protein
Vinculin in response to a mechanical
force~\cite{23,25,64,65}. We showed that the
mechanosensitive domain of ${\upalpha}$-Catenin is required for proper
distribution of PI3K, a kinase controlling the formation of protrusions
and cell orientation~\cite{34}. We then quantified the cellular
distribution of ${\upalpha}$-Catenin and \mbox{observed} that it accumulates
mainly at the posterior side of the cells, where there is contact with
protrusions formed by follower cells. Using laser ablation, we observed
that these protrusions are indeed under tension, and that this tension
requires the adherens junction protein E-Cadherin.

Thus, we showed that polster cells are able to detect the migratory
activity of a following cell and align with it and proposed to name
this phenomenon ``guidance by followers''. Using numerical simulations,
we verified that guidance by followers is sufficient to account for the
collective guidance of a group of cells (the polster) by oriented
following cells. Importantly, varying the speed of the following cells
in the simulations, we observed that the polster would always match its
migration speed to the elongation of the posterior mesoderm thanks to
this guidance mechanism. We could prove experimentally that this
prediction is correct, suggesting that guidance by followers, on top of
ensuring collective guidance of the polster, also guarantees robust
elongation of the axial mesoderm, preventing separation of the two
tissues during gastrulation.

Based on these observations, we proposed a mechanistic model for
polster migration and coordination with posterior mesoderm extension
during axial mesoderm elongation (Figure~\ref{fig4}). During
gastrulation, the posterior mesoderm undergoes convergence and
extension. At the contact between the two tissues, a cell from the
front row of posterior mesodermal cells forms a protrusion that
contacts a polster cell. This protrusion forms an adherens junction
then builds up tension that recruits and opens ${\upalpha}$-Catenin in
the polster cell. This provokes redistribution of PI3K activity in this
cell at the opposite side compared to the contact, leading to the
alignment of polster cell polarity with those of the posterior cell. In
turn, this polster cell will form protrusions and orient a cell from
the next row and so on until the whole tissue is oriented away from the
posterior mesoderm and migrates efficiently towards the animal pole of
the embryo.

\begin{figure*}
\includegraphics{fig04}
\caption{\label{fig4}\fontsize{9.5}{12}\selectfont 
Mechanistic model for guidance by followers
organizing polster collective migration. A polster cell contacted by a
following cell detects tension generated by the active migration of the
follower through mechanosensation. This orients the migration of the
contacted cell which, in turn, orients the cell in front of it so that
the directional information propagates through the entire group.
Adapted from~\cite{7}, all rights reserved.}
\end{figure*}

\section{Perspectives}

The full mechanism that leads to guidance by followers is not yet
elucidated, but several leads are open for understanding this
phenomenon in more detail. In a recent article, we studied what might
be the outcome of conflicting information on polster collective
migration~\cite{35}. We proposed a development of the simulations,
testing different implementations of guidance by follower response upon
multiple\break collisions. Although the different models performed almost
equally well, the model proposing that leading cells align with the
cell presenting the largest surface of contact seems to fit the
experimental data slightly better. Controlled interaction between cells
may provide more experimental input to understand how a cell integrates
multiple stimuli.

We have shown that mechanosensation of neighboring cell protrusions is
required for polster cell\break orientation. However, the distribution of
forces in the polster is still unknown, as is their amplitude. To
better understand how cells orient in response to forces applied by
neighbors, it would be necessary to describe the mechanical state of
the tissue at different scales. Preliminary data using small deformable
PDMS beads as tissue scale force sensors suggest that there is a
front-to-rear gradient of anisotropic tension and that the maximal
tension seems to be aligned with the direction of
migration~\cite{48}. However, a finer resolution of forces might be
necessary to understand the force applied and experienced by the cells
for example by using molecular FRET tension sensor
modules~\cite{21}.

From a molecular point of view, more functional analyses would be
necessary to understand how cells are applying forces through their
protrusions and how the opening of ${\upalpha}$-Catenin triggers
orientation of cells. Indeed, several signaling pathways are known to
be required for polster cell orientation, like Wnt/Planar cell polarity
(PCP), PI3K, and E-Cadherin~\cite{18,27,34,58}. In Medaka,
another fish model organism, FGF signaling has also been reported as
necessary for proper polster migration~\cite{47}. How all these
pathways are interrelated is still an open question, but a first
interesting observation is that several of them are common to those
described in other instances of contact regulation of locomotion. For
instance, contact inhibition of locomotion described in neural crest
cells relies on the formation of N-Cadherin adherens junction and
activation of the Wnt/PCP pathway that locally activates the small
GTPase RhoA, leading to the collapse of the protrusion and the
formation of another protrusion at the opposite side of the
cell~\cite{50}. Similarly, contact following of locomotion relies on
the Wnt/PCP pathway as its loss of function abrogates collective
behavior~\cite{29}.\looseness=-1

Despite these areas of uncertainty, the newly identified mechanism,
guidance by followers, represents a significant step forward in
understanding collective cell migration. It adds to our insight into
how mesenchymal cells can communicate and how they organize to migrate
as a group. Moreover, given its proximity to other instances of contact
regulation of locomotion, it suggests the existence of a toolbox that
cells use to communicate at contact sites, which involves pathways such
as the Wnt/PCP pathway and Cadherin-mediated junctions.

Furthermore, this discovery helps to understand how different tissues
coordinate and orient their movement in the complex environment of a
developing embryo. Guiding a tissue with a chemotactic gradient over
long distances in a dynamic environment could prove very complex.
Similarly, ensuring the relative motion of different tissues that move
by different mechanisms could be a challenging task. Guidance by
followers allows one tissue to guide another, which is an efficient
solution for robustly coordinating tissue movement.

Finally, guidance by followers might provide insight into how groups of
cells manage to migrate without apparent external guidance cues, such
as streams of metastatic cells leaving a tumor. With guidance by
leaders, metastatic cells would require an external guidance cue to
efficiently migrate. On the contrary, if cells are oriented by their
immediate followers, then an arbitrarily long column of cells could
theoretically be guided by an initial asymmetry at one end. Adding new
cells exiting the tumor would thus orient the last row of the stream,
then orient the next row, and so on. Further work might thus identify
mechanisms similar to guidance by followers in other systems.
\looseness=-1

\section*{Declaration of interests}
The authors do not work for, advise, own shares in, or receive funds
from any organization that could benefit from this article, and have
declared no affiliations other than their research organizations.

\section*{Acknowledgements}

I thank Sophie Escot, Am\'{e}lie Elouin, Diego Jahn, Sebasti\'{a}n
Gonz\'{a}lez-Tirado, J\"{o}rn Starru\ss, Lutz Brusch for the help, and
Nicolas B. David for the supervision on the work described in this
article. I am also grateful to Nicolas B. David, Manon Valet, Ana\"{i}s
Bailles, Roudaina Boukheloua and Giulia Serafini who critically read
the manuscript. This work was supported by a fellowship from the
Alexander von Humboldt foundation.

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