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Universitas Odontológica

ISSN: 0120-4319
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Pontificia Universidad Javeriana
Colombia

Bayona Rodríguez, Francy

Embryonic development of the central nervous system and sense organs: a review
Universitas Odontológica, vol. 31, no. 66, January-June, 2012, pp. 125-132
Pontifical Javeriana University
Bogota Colombia

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 Embryonic development of the central nervous
system and sense organs: a review
Embryonic Central Nervous System and Sense Organ
Development: Review
Francy Bayona Rodríguez
Dentist, specialist in
Orthodontics, student of Master of
Dentistry, Institute of Genetics,
National university of Colombia,
Bogota Colombia.
The article is one of the products of the author's
Master of Dentistry work at the
National university of Colombia.
HOW TO CITE THIS ARTICLE
Bayona F. Embryonic development of the system
central nervous and sense organs: review.
Univ Odontol. 2012 Jan-Jun; 31 (66):
125-132
Received for publication: 02-20-2012
Accepted for publication: 04-03-2012
Available at http://www.javeriana.edu.co/
dental university
125
BASIC SCIENCES, BIOTECHNOLOGY AND BIOINFORMATION
Univ Odontol. 2012 Jan-Jun; 31 (66): 125-132. ISSN 0120-4319
ABSTRACT
The nervous system originates from the ectodermal germ layer. Just as in postnatal life the
nervous system is clearly differentiated into a central and peripheral nervous system, in its
embryonic stage the formation of each follows different but close paths. This review
emphasizes the formation of the central nervous system and specific structures, such as the
sense organs. A brief journey through processes such as gastrulation, neuralization and
placode formation is presented until reaching the different structures that make up the central
nervous system and the sense organs.
KEYWORDS
Nervous system, central nervous system, peripheral nervous system, neuralization,
gastrulation, placodes.
THEMATIC AREA
Embryology.
ABSTRACT
The nervous system has its origin in the well-known ectodermic germinal layer. During the
postnatal life, the nervous system is clearly differentiated in central nervous system and
peripheral nervous system. During the embryonic stage, all the components follow different
paths but they are still close to each other. This review focuses on the central nervous system
and development of the sense organs. It includes a brief review of processes such as
gastrulation, neurulation and development of cranial placodes and the structures that make
up the central nervous system and the sense organs.
KEY WORDS
Nervous system, central nervous system, peripheral nervous system, neurulation, gastru-
lation, placodes.
THEMATIC FIELD
Embryology.
 INTRODUCTION

From the anatomical point of view, the nervous system is made up of the central
nervous system (CNS), made up of the brain and the spinal cord; by the peripheral
nervous system (PNS), formed by the cranial and spinal nerves, and by the
126
peripheral ganglia (1-3).
Bayona F.

Generally speaking, the nervous system originates from the ectodermal germ
layer. Part of this ectodermal layer gives rise to, first, the neural crest cells (CCN),
Univ Odontol. 2012 Jan-Jun; 31 (66): 125-132. ISSN 0120-4319

which contribute to the formation of the SNP (Schwann cells, some neurons, glial
cells, and the sympathetic and parasympathetic nervous system); second, to the
neuroectoderm, which originates the generating neural tube of the CNS (brain,
spinal cord, some neurons, oligodendrocytes, astrocytes and motor neurons),
and, third, the ectoderm anterior to the neural plate or non-neural ectoderm from
which the placodes originate cranial organs, which form the specialized sensory
organs and the ganglia of some cranial nerves (2,4-6).

This is a brief description of the most important events in the initial formation of
the nervous system and the organs of the senses, a topic of importance for the
formation in basic sciences of dental students, of their specialties and of those
other areas that they wish. delve into the area of craniofacial developmental
biology. It is important to remember that most of these events occur during the
same period of embryonic life, between the third and fourth weeks.

CENTRAL NERVOUS SYSTEM

To describe the formation of the CNS, different key stages are described such as:
gastrulation, neuralization and the establishment of primary and secondary
vesicles.

Gastrulation and differentiation of neuronal progenitor cells

During the third week of gestation in humans, an important event called
gastrulation7). During this process, the embryo goes from being a structure
organized in two layers (epiblast and hypoblast) to one formed by three layers
(ectoderm, mesoderm and endoderm).
(7). At this stage, the first sign of the formation of the nervous system appears: the
establishment of the neural plate (8) (Figure 1).

Figure 1
Gastrulation: establishment of the three germ layers in the embryo

Note. Establishment of the three germ layers in the embryo: ectoderm (blue), mesoderm
(orange) and endoderm (green stripes). In purple: notochord. The plate
neural is formed thanks to the induction of cells that migrate under
the epiblast through Hensen's node and the primitive streak, to
become endoderm and mesoderm. Hensen's node acts as an
organizing center, and is defined as a group of cells that emit
signals capable of inducing and collaborating in the establishment
of the embryonic tissue pattern (9). The signals emitted by this
organizing center, by the primitive streak and by the notochord
induce the differentiation of the cells located in the midline anterior
to Hensen's node, turning them into neural progenitor cells that
form the neural plate (2,8,10) . During this process, inhibitory
signals from bone morphogenetic proteins (BMP) and other types
of genes such asObelix, ERNI, Churchill, Wnt, among others. When
BMP inhibitors are present, ectodermal cells expressSox3,
important marker of the proneural plate (9). This event is important
because it marks the moment and the site of cell signaling that
gives rise to the different cell destinations of the ectodermal cells
that will become the nervous system. Source: self made.
Neuralization
Towards the end of the third week, when gastrulation is
ending, the neural plate undergoes changes that lead to
the formation of the neural tube. This process is called
neuralization (Figure 2) (2,11).
Figure 2
Neuralization
Note. Formation of the neural tube. Nonneural ectoderm (red),
neuroectoderm (pink), and neural crest cells (green) are clearly
established. In light purple: somites, purple: notochord.
Source: self made.
Neuralization occurs in two forms: primary neuralization,
which occurs in the anterior part of the plaque, and
secondary neuralization, which occurs in the most
posterior part of the plaque. In the primary, the cells of the
neural plate proliferate and rise, until they become the
neural folds, which fuse to form the neural tube. During
high school, the tube initially forms as a
dense bar that is subsequently hollowed out to form the
secondary neural tube (2).
Neuralization segments the ectoderm into three cell
groups: the one that remains directly in the tube, known as
127
the neural ectoderm or neuroectoderm; the one that
covers the neural tube, called the non-neural ectoderm,
CNS embryonic development
and the one that is initially located between these two and
later migrates to different destinations, the CCN (Figure 2).
Univ Odontol. 2012 Jan-Jun; 31 (66): 125-132. ISSN 0120-4319
The neural tube closes as the folds meet in the dorsal
midline. Simultaneously with this closure, detachment or
delamination occurs and then the migration of the CCNs.
This event is variable between species; in some it is carried
out once the tube has been closed, while in others it
begins before the union of the neural folds (2,4). The same
variability applies to the formation and closure of the tube,
since it does not occur simultaneously along the
anteroposterior axis, nor in the same way between the
different species (8).
The open ends of the neural tube are called the anterior
and posterior neuropore. Once the closure of the
neuropores has finished (gestation day 26 for the anterior
and 28 for the posterior, approximately), the neural tube is
seen as a closed cylinder separated from the superficial
ectoderm and secondary neuralization occurs (8). This
neuralization is also variable between species: in chicken,
somite 25 is flowed, while in humans it affects only the
sacral area (2,4). Another particular characteristic of
secondary neuralization is that although neural folds do
not form at this level, the secondary neural tube has been
shown to delaminate neural crest cells (2).
Some studies suggest that the Sonic Hedgehog (shh) gene
orchestrates neural tube morphogenesis, coordinating cell
adhesion and mobility with proliferation and
differentiation (12,13).
Formation of primary and secondary vesicles
Before finalizing the closure of the neural tube, a
macroscopic differentiation begins. This occurs as changes
in the anterior end of the anterior neural tube, which
causes the primary vesicles. These vesicles are identified
as: the forebrain or forebrain, the midbrain or midbrain,
and the hindbrain or rhomboencephalon, separated from
each other by valleys or constrictions (Figure 3). The
remaining neural tube becomes the spinal cord. In
mammals, it ends before the end of the vertebral canal
and continues in a chain of tissue without neurons called
 the filum terminale (2). This area is characterized by the fact that Figure 4
it appears to be capable of generating glial cells and melanocytes, Secondary vesicles and der structures ivadas
but not neurons (2,14).

Figure 3
128 Primary vesicles Forebrain 1
yona F.

0-4319

Midbrain 3

Rhomboencephalt 5

1. Telencephalus: cerebral hemispheres and lateral ventricles. 2.

Diencephalon: thalamus, hypothalamus, third ventricle.
3. Midbrain: Silvio aqueduct. 4. The metancephalon and
Univ Odont

Note. In yellow: procensephalon; orange: midbrain; light green: myelncephalon: cerebellum, brainstem, fourth ventricle. 5. Spinal
rhomboencephalon; dark green: pith; purple: notochord. Source: self cord
made. Source: self made.

Neural tube segmentation establishes sites such as the Figure 5

isthmus and the zone intratal limitstomica, that behave as Rhomboencephalon segmentation (rhombomers 1 to
7), direction of migration of CCN towards the
secondary organizing centers and generate the molecular
gill arches
signals that give rise to the different cell subtypes (4,6,8). At
the time of posterior neuropore closure, the optic vesicles
have spread laterally on each side of the forebrain,
specifically the diencephalon (4). These optic vesicles are part
of the secondary vesicles. The forebrain is subdivided into
two secondary vesicles, an anterior one called the
telencephalon and a posterior one, the diencephalon. The
telencephalon forms the cerebral hemispheres with the
lateral ventricles; while the diencephalon generates the
thalamic and hypothalamic regions and the third ventricle.
The midbrain is not divided and its light originates in the
cerebral aqueduct or aqueduct of Silvio.

Source: self made.

On the other hand, the rhomboencephalon is subdivided into

the metancephalon, located in the most anterior part of the
Organization of the neural tube
The organization of the neural tube in an
hindbrain, origin of the cerebellum, and in the
anteroposterior direction is clear; however, there is
myelncephalon, which forms the brainstem. Both vesicles
another axis as important as that: the dorsoventral.
that form the fourth ventricle (figure 4) (4). There is a
Dorsoventral polarization is key to the development and
peculiarity regarding the segmentation of the hindbrain or
differentiation of neuronal types. According to the
rhomboencephalon, and that is that it is subdivided into
molecular signals that each area of the tube receives, it
small compartments called rhombomers. The cells of the
is also its cellular specification. The most dorsal part of
rhombomers have an interesting behavior, since they do not
the tube is specialized in developing sensory neurons,
mix with each other, despite their closeness. On the other
while the ventral portion is in charge of motor neurons.
hand, the cells immediately superior to the rhombomeres,
This dorsoventral polarity is given by signals from the
belonging to the neural crest, form specific tissues
surrounding tissue, which make the tube regionalize
depending on where the rhombomere comes from (figure 5)
(15).
in parent domains. Each domain is characterized by the expression of a specific
type of transcription factors, among other molecules, which thus give identity to
the different neuronal subtypes (12,13,16). The ventral area is under the influence
of proteins such as SHH from the notochord, while the dorsal area is influenced by
proteins of the transforming growth factor superfamilyβ (TGF-β), generated by the
129
epithelial ectoderm that covers the tube (12,13,16).

CNS embryonic development

Initially, the tube is a layer of neurogerminal epithelium, that is, it is a layer one

Univ Odontol. 2012 Jan-Jun; 31 (66): 125-132. ISSN 0120-4319

cell thick composed of neural stem cells (8). These cells are initially capable of
dividing until they reach a point where they no longer do so, migrate from the
neural tube and differentiate into neurons or glial cells to form the SNP (4). This
cell division is done vertically. This means that a daughter cell remains close to the
lumen of the tube and the other towards the external surface, from where they
migrate easily. As cell division continues, the daughter cells that remain form a
mantle or intermediate zone and the germ layer becomes the ventricular zone
and later the ependyma (Figure 6). The cells of the intermediate zone can
differentiate into neurons and glia.

Figure 6
Dorsoventral organization of the neural tube

Source: self made.

At this point in development, neurons connect with each other and send their
axons out of the lumen of the tube, making the marginal zone a cell-poor zone.
Later, the glial cells cover the axons in the marginal zone with myelin sheaths,
which give a whitish appearance. For this reason the intermediate zone that
contains the neuronal bodies is calledGray matter, and the axonal marginal layer,
white matter4.8). The organization of these three layers is maintained during
development, only that the intermediate zone assumes a butterfly shape
surrounded by white matter and a longitudinal fissure is formed, the limiting
groove, which divides the tube into the dorsal half and the ventral half or wing
plate and baseline, respectively (figure 6) (4).

In the cerebellum some neuronal precursors enter the marginal zone to form
clusters of neurons called nuclei. Each nucleus functions as a unit that acts as a
way station between the outer layers of the cerebellum and the other parts of the
brain. Other neuronal precursors migrate out of the germinal epithelium and
form a new layer, called
 outer granular layer. Neuroblasts that proliferate from the
outermost part of this layer contact bone morphogenetic
proteins (BMPs) and differentiate into granular neurons
capable of migrating back to the ependymal area and
generating the inner granular layer. Meanwhile, the
130
ependymal area generates different types of neurons and
glial cells, including Purkinje neurons, the most common in
Bayona F.
the cerebellum. These cells, in turn, support the division of
precursors of granular neurons in the outer granular layer
Univ Odontol. 2012 Jan-Jun; 31 (66): 125-132. ISSN 0120-4319
through the secretion of SHH.
Finally, in the brain the three initial layers of the neural
tube are also modified as in the cerebellum. Certain
intermediate zone neuroblasts migrate through white
matter to form a second zone of neurons on the outer
surface of the brain called the neocortex (also gray
matter). This is stratified into six layers of neuronal bodies
with functional differences. Additionally, the cerebral
cortex is horizontally organized into more than forty
regions that anatomically and functionally regulate
different processes (4).
Peripheral nervous system and sense
organs
The SNP of the cranial region comprises the sensory
ganglia, made up of sensory neurons and cranial nerves
(17). Sensory ganglia originate from the CCN and
ectodermal placodes (17,18). Although both components
come from the rim of the neural plate, the placodes are
restricted to the cephalic area, while the CCNs are
distributed throughout the embryo, making them the
exclusive tissue of the peripheral ganglia of the trunk.
(18). Cells derived from this cranial sector of the embryo
respond to the regulation of the anterior neural border
(ANR), where fibroblast growth factor8 (Fgf8) plays an
important role, as well as BMPs from CCNs (6).
Placodes are transitory thickenings of the cranial
ectodermal tissue and are formed by apicobasal
elongation of cuboidal cells in the inner layer of the
ectoderm (17-20). Cranial placodes include the anterior
pituitary, olfactory, lens, trigeminal, otic, and epibranchial
in humans (17-20). They begin their formation shortly after
gastrulation, and depending on their position on the
anteroposterior axis and the influence of the surrounding
tissue, they acquire a specific identity. They have two ways
of becoming specific derivatives: by invagina-
tion and subsequent delamination of the thickened
epithelium in the case of the anterior pituitary, lens, otic
and olfactory; or only by delamination of cells to
underlying tissues, as occurs in the trigeminal and
epibranchial tissues (17,18) (figure 7). Placodes are not just
signal receptor structures, but as they develop they
become signal generators for nearby structures (17).
Ffigure 7
Fplacode formation
A) Intact ectoderm. B) Thickening of the ectodermal layer as the
beginning of placode formation. C) Placode formation by
ivagination, which causes adenohypophysial, lens, optic and
olfactory placode. D) Formation of placodes by delamination, which
creates trigeminal and epibranchial placodes.
Source: self made.
They can be sensory, which contribute to the formation of
the eyes, the acoustic-lateral system and olfactory organs,
or they can be neurogenic, forming sensory neurons of the
cranial ganglia (17,18). All placodes, except for the lens and
the anterior pituitary, originate neurons, in addition to
other cell types. Neurogenic ones are divided into two
types, according to their location and destination:
dorsolateral (trigeminal and otic), which occupy a relatively
dorsal and lateral position to the hindbrain, and
epibranchial, located ventrally to the otic placode and
dorsocaudal to the pharyngeal clefts (17,18,20).
Sensory neurons of the ophthalmic and maxillomandibular
lobes of the trigeminal ganglion (cranial nerve V) are
generated from the trigeminal placode. The precursors of
the sensory epithelium of the inner ear and neurons of the
olfactory nerve (VIII cranial nerve) are formed from the otic
placode. The epibranchial placodes (geniculate, petrous
and nodose) give rise to the viscerosensory neurons of the
facial (VII), glossopha-
rhingeal (IX) and vagus (X). These neurons innervate
internal organs to transmit information such as heart rate,
blood pressure, and abdominal distention from the
periphery to the CNS. More specifically, epibranchial
placodes contribute only to viscerosensory neurons in the
distal ganglion of cranial nerves VII, IX, and X, innervating
viscerosensory organs and taste buds (Figure 8). The
proximal ganglia of these nerves come from the CCN and
produce somatosensory neurons (18). This is how the
ganglia of the cranial nerves are formed by the meeting of
neuroblasts from the different placodes. This formation is
regulated by genetic and molecular signals from nearby
tissues, such as the CCN and the pharyngeal endoderm.
Figure 8
Distribution of placodes with the most representative
sensory derivatives in somite stage 10 of the embryo.
of chicken
Note. In blue: olfactory placodes; green: placodes of the lens; yellow
and red: trigeminal placode; orange: otic placode; purple:
epibranchial placodes.
Source: self made.
On the other hand, the adenohypophysial placode
originates the anterior lobe of the pituitary gland and the
endocrine secreting cells of the pituitary. The olfactory
forms the olfactory epithelium of the nose and the axons
of the sensory neurons, which project to the olfactory bulb,
vomeronasal organ, and terminal nerves; in addition, it
forms glial cells, which enter and migrate to the brain
(17,18,20).
The latter is the only placode capable of producing glial
cells, since most are of CCN and neuroectoderm origin.
The placode of the lens differs into the lens. The
development of the latter depends on the mutual
interaction between the cup
optic and lens vesicle. This process has been well regulated
thanks to a master molecule, the transcription factorPax6.
The molecular precursors for the most anterior placodes
131
(adenohypophysial, olfactory and lens) are located in the
most anterior preplacodal region, while the precursors of
CNS embryonic development
the others are located more caudally. This division is
evidenced by the expression of transcription factors, which
Univ Odontol. 2012 Jan-Jun; 31 (66): 125-132. ISSN 0120-4319
divides these areas into small subdomains that each
express a transcriptional code that determines their
placodal identity. These genes include transcription factors
such asSix1, which is initially expressed in the entire
preplacodal area; Pax8, expressed in the posterior domain
of the preplacodal sector, which are precursors of the otic
placode; Dmrt4,
expressed above for the zones that will be olfactory, lens
and adenohypophysial placodes;
Foxi1c, identified in the primordia of the epibranchial
placodes; Pax6, expressed in the neural plate and in the
precursors of the lens and olfactory placodes, and Ngnr1,
expressed in the trigeminal placode. As development
proceeds and the placodes separate, the combination of
expressed genes changes. New genes such as Tbx2 are
activated in the trigeminal and otic placode and Lens1,
restricted to the lens placode. Thus we can see that among
the regulatory factors for placode development are the Six,
Eya and Pax gene families, expressed in all vertebrate
sensory placode. It is important to clarify that these genes
are not only expressed in their respective placodes, but
also in their derivatives (17,18,21-23).
CONCLUSIONS
The formation of the nervous system is given by a series of
highly specialized processes, with some aspects still to be
clarified. Its origin is the ectodermal layer, which is under
the influence of various molecular signals that define its
identity. In this way the neural, preplacodal or CCN
ectoderm and thus its various derivatives are established.
Different classes of signaling molecules are involved in the
induction of different cranial nerve structures, and among
them the most important molecules are SHH, BMP,
fibroblast growth factor (FGF) and WNT.
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