MS - ORTHODONTICS

Intrauterine
Period of
Development
John Patrick F. Baluyut D.M.D.
Initial stages of embryonic development from time of fertilization to
implantation in the uterine mucosa
Stages of Fetal Development
 Intrauterine Period

Fetal Period

Preimplantation • From the ninth week of the term

Embryonic Period • Characterized by growth and
Period
expansion of already established
From the seventh day to the eighth week
body structures with a little
The first 7 days following fertilization after fertilization
differentiation or new-organ
formation
• Establishment of ossification centers
and the starting of fetal movements
 Intrauterine Period
Embryonic Period
can be further
divided into:

Pre-Somite Phase Somite Phase Post-Somite Phase

• Encompasses the second and third • Lasts from the 21st to the 31st day • Lasts from the 32nd to the 56th day
weeks after fertilization • Characterized by formation of the • Characterized by the development
• Characterized by differentiation of dorsal metameric segments of the of external body features and further
the three germ layers body development and differentiation of
• Formation of the embryonic adnexa • Establishment of the basic body the basic structure
from the inner cell masses plan, polarity, and patterns of the
major organ systems
 Chronological
Sequence of Events
During the Embryonic
Period
Selected Carnegie
Stages of Human
Embryonic
Development from
28th to 56th day
Pre-Implantation Period
Pre-Implantation 01 During the first 2-3 days, the single-
celled zygote divides progressively to
form a 16-celled struture called a

Period 02
blastocyst

Blastocyst
• Fluid filled cavity which divides
Intrauterine Period the cells into the outer sphere of
cells and an inner cell membrane

Outer Sphere of Cells - Forms

03
Trophoblast
Inner Cell Mass - Forms Embryo
 Pre-Somite Period 01 During the second week two
important events occur:
(14- 21 days) • Trophoblast differentiats into a
bilaminar structure which
contributes to the formation of
Intrauterine Period chorionic villi
• Inner Cell Mass divides to form a
bilaminar structure

02 Bilaminar Structure
• Epiblast (Ectoderm)
• Hypoblast (Endoderm)

03 A coelomic cavity develops in the

extraembryonic mesoderm which
enlarges progressively to surround the
embryo completely except at the stalk
 Pre-Somite Period 01 By the end of the second week
• Axis of the embryo starts to grow
(14- 21 days) with the appearance of the node at
the rostral end

Intrauterine Period
02 Formation of the primitive node and
primitive streak defines the axis of the
embryo
• Develops under the signalling
influence of the genes
⚬ Hedgehog
⚬ Nodal
⚬ FGF
⚬ Wnt
03
⚬ BMP
 Pre-Somite Period 01 The activity of the node contributes to
lefward fluid flow which causes
(14- 21 days) development of Left-Right asymmetry
in the developing embryo

Intrauterine Period

02
Localized thickening of the endoderm
at the midcephalic region gives rise to
the pre-chordal palte under the
influence of the Sonic Hedgehog
• Shown to have a head-organising
or molecular organzing function
03
 Pre-Somite Period
(14- 21 days)
Intrauterine Period
 Pre-Somite Period 01 The pre-chordal layer also contributes
an endodermal layer to the
(14- 21 days) oropharyngeal membrane

Intrauterine Period
Early in the third week
02
• Epiblast proliferates and
differentiates to give rise to the
third layer of cells called the
mesoderm through a process
called Gastrulation

03
The proliferation of the epiblast starts
at the caudal end of the embryo
leading to the formation of the
Caudocranial groove
 Pre-Somite Period
(14- 21 days)
01 By the end of the third week
• Mesoderm layer is well
Intrauterine Period
established and separates the
ectoderm and endoderm
throughout the embryo
⚬ Except in the cloacal
membrane in the caudal
region
⚬ pre-chordal plate at the
cranial midline area
 Pre-Somite Period 01 Cells of the primitive streak
proliferate further in the cranial
(14- 21 days) direction and contact the pre-chordal
plate

Intrauterine Period
Formation of the Notochord
02
• Represents early the midline axis
of the embryo helping to establish
the axial skeleton
• Induces formation of the neural
plate in the overlying ectoderm
which later gives rise to the neural
03 ectoderm
 Somite Period 01 Charaterized by establishment of the
primordia of most of the important
(21- 31 days) organ systems
• Gut
• Kidneys
Intrauterine Period • Lungs
• Adrenals
• Heart

02 Between this period the embryo

changes form from a flat disc to a
tubular structure

03 Rapid growth of the developing

central nervous system on the dorsal
aspect leads to folding of the embryo
over its ventral aspect
Genetic Regulation of Somitic
Development: Notch Signaling

Formation of the axial and appendicular

skeletal elements in the body are under
tight control between osteoblastic and
osteoclastic activity

• Principal genes that are involved in this

process are found in the pre-somite mesoderm
⚬ Wnt
⚬ FGF-FGFT
⚬ Notch signaling pathways
Genetic Regulation of Somitic
Development: Notch Signaling
• Controlled osteoblastic activity is also closely
regulated by the inhibitory actions of notch on
developing osteoblasts
• Done by the inhibitory action of notch on
osteoblastic markers
⚬ Alp
⚬ Ocn
⚬ Col1A1
⚬ Runx2
• Similar actions of notch on osteoclastogenesis
have been documented by its activation
ofRANKL and OPG
Neurulation
Process of development of the neural
plate, neuroectoderm, and the neural
tube

• During the third week of development, the

notochord induces the overlying ectoderm to
thicken and differentiate into the neural plate
⚬ Chordamesoderm - Median strip of
mesodermal cells extending through the
length of the embryo which is responsible
for developing the organization plan of
the head
⚬ Pre-Chordal Plate - Anterior region plays
a significant role in inducing neural plate
formation
Neurulation

Process of Neurulation can be divided

into:

• Primary Neurulation
⚬ Associated with the formation of a hollow
tube by the proliferation of cells of the
neural plate
• Secondary Neurulation
⚬ Leads to formation of the medullary
cavity (Neural Tube) from a solid core of
cells

*A few important genes essential for neural tube

formation include Pax3, SHH, and Open Brain
Neurulation
Neural Tube consists of three sets of
cells:

• Inner layer of cells which

⚬ Form the future spinal cord and the brain
• Neural crest cells
⚬ Migrate across the embryo eventually
⚬ Have a significant role in development of
the facial structure apart from the
peripheral neurones
• Epidermal cells
Neurulation

Stages:

• Formation of the Neural plate

• Shaping of the Neural plate
• Bending of the Neural plate to form the
Neural Groove
• Closure of the Neural Groove to form the
Neural Tube
Neurulation

• At around the 20th day post-conception

⚬ Lateral edges of the neural plate elevate to
form the neural folds which enclase a
neural groove in the midline
• At the 22nd day post-conception
⚬ Neural folds start to fuse with the
counterpart of the other side over the
neural groove
Neurulation

Neural Tube

• Primordia of the central nervous system

• Anterior end enlarges to form the three
segments of the brain
⚬ Forebrain
⚬ Midbrain
⚬ Hindbrain
• Around this time also the lens and otic
placodes begin to form as outgrowths from the
ectoderm at the cranial end of the embryo
Development of Neural Crest

Refers to a special collection of cells that

arise in the crest of the neural folds
during the process of neurulation

• Consists of pluripotent cells,

ectomesenchymal in origin, induced by:
⚬ Wnt Activation
⚬ BMP inhibition Signal Pathways
• Characterized by their tendency to extensively
migrate along the natural cleavage planes
between the three germ layers
Development of Neural Crest

• They divide as they migrate giving rise to cell

masses that are much bigger at the destination
than at their origin
• They differentiate into specific tissues
according to their morphogenetic fields and
give rise to many important tissues both in the
head, neck and trunk
Development of Neural Crest
Varieties of Neural Crest Cells,
According to their Final Destination and
Differentiation:

• Cranial Neural Crest Cells

⚬ Give rise to structures in the head and
neck
• Trunk Neural Crest Cells
⚬ Form melanocytes and dorsal root ganglia
of sensory nerves
• Vagal and Sacral Neural Crest Cells
⚬ Generate parasympathetic ganglia
Development of Neural Crest

Varieties of Neural Crest Cells,

According to their Final Destination and
Differentiation:

4. Cardiac Neural Crest Cells

⚬ Develop into melanocytes, neurons,
cartilage, and connective tissue (of the
3rd, 4th, and 6th pharyngeal arches)
⚬ Produce musculoconnective tissue of the
large arteries arising from the heart
Neural Crest Cells
Development of The Skeleton
The intraembryonic mesoderm
differentiates into three types of cell
masses depending upon:

• Lateral plate Mesoderm

⚬ Gives rise to the heart, blood vessels, and
blood cells
• Intermediate Mesoderm
⚬ Connects the paraxial mesoderm with the
lateral plate
⚬ Differentiates to form the gonads,
kidneys, and adrenal glands
• Paraxial Mesoderm
⚬ Craniofacial structures
Development of The Skeleton
Development of The Skeleton

Paraxial Mesoderm

• Develops adjacent to the notochord along the

dorsal surface of the embryo
• Its rostral end gives rise to elevated masses of
tissues in the cranial region called
Somitomeres
• Its cranial end gives rise to structures called
Somites
Development of The Skeleton
Somites

• Sclerotome
⚬ The ventromedial part gives rise to the
vertebral region except in the occipital
region
• Dermatome
⚬ Lateral part gives rise to the dermis of the
skin
• Myotome
⚬ Intermediate part gives rise to the muscles
of the trunk and limbs and some
craniofacial muscles
Pharyngeal Apparatus
Consists of a series of bilaterally paired
arches, pouches (clefts), grooves, and
membranes

• Seen as paried tubal elevations on the ventral

surface of the embryo on each side of the
midline
• Partially separated on the external surface of
the embryo by fissures called pharygeal
grooves or clefts
• Pouches are partially separate on the arches on
the internal aspect
• Pharyngeal membranes represent the tissue
interposed between the pouches and clefts and
connect adjacent arches
Pharyngeal Apparatus

Pharyngeal Arches

• Development of the tissues of the neck and the

face is largely dependent on mesoderm of the
cranial somitomeres
• Formed by cells of the somitomere mesoderm
and the mesoderm of the lateral plate
• Outgrowths on the ventral surface of the
rhombencephalon during the fourth week of
intrauterine life
Pharyngeal Apparatus
Pharyngeal Arches

• Each pharyngeal arch has its specific

apparatus
⚬ Forms the skeleton of the arch
⚬ Nerve that supplies the muscle and
mucosa derived from the arch
⚬ Artery (Aortic Arch)
• All these components are well developed in
the first and second arches except for the
arteries
• The pharyngeal arch play a major role in
formation of the face, oral cavity, teeth nasal
cavity, pharynx, larynx, and neck
Pharyngeal Apparatus
Derivatives of Pharyngeal Arches
Pharyngeal Apparatus
Derivatives of Pharyngeal Pouches
Genetic Influences in
Pharyngeal Arch Development
and Expression
Endoderm is the most important organizer of pharyngeal arches
• TbX1 Gene
⚬ Specific to endodermal derivatives
⚬ Key gene regulating formation and development of pharyngeal arches
⚬ Influenced by retinoic acid
• FGF signaling
⚬ Known to play a key role in endoderm pouch formation and differentiation
• FGF and Wnt Signaling
⚬ Have been shown to be important in endodermal pouch formation and pharyngeal segmentation
Genetic Influences in
Pharyngeal Arch Development
and Expression
Endoderm is the most important organizer of pharyngeal arches
• D1x Family
⚬ Comprises six genes that are expressed in the pharyngeal arches during development and differentiation
• D1x1 and D1x2
⚬ Specifically expressed in the proximal segment of the first pharyngeal arch
⚬ Problems in these cause developmental malformations in the upper and lower jaws
• D1x5
⚬ Problems here cause malformation of Meckel's Cartilage
Genetic Influences in
Pharyngeal Arch Development
and Expression
Endoderm is the most important organizer of pharyngeal arches
• Edn/D1x/HAND Signaling Axis
⚬ Regulate the first pharyngeal arch patterning
⚬ Upper and lower jaw formation
• Hox Genes
⚬ Play a role in body plan organization along the anterior-posterior axis
⚬ Not expressed in the first pharyngeal arch
⚬ Expressed in the neural crest cells of the second to sixth pharyngeal arches
⚬ Each pharyngeal arch is under control of one Hox group gene

*DIx Genes influence first pharyngeal arch

*Hox Genes influence the second to sixth pharyngeal arch
 Post - Somite Period 01
Characterized by the growth and
morphodifferentiation of previously
(32- 56 days) established organ systems

Intrauterine Period
Head becomes large and pre-
02
dominates over the small body

Somites become less conspicuous on

03 the external surface

Face starts to show development of

04 the eye, ear, and nose which starts to
resemble the human form
 Post - Somite Period 05 Limb buds start to grow
(32- 56 days)
First fetal muscular movement may
Intrauterine Period 06 occur at the later end of the stage
Fetal Stage
• Characterized by rapid growth of organ
systems previously established
• Little differentiation of new-tissue systems is
seen
• Main emphasis remains in the differential
growth of various systems
• Establishment of primary ossification centers
also occur at this stage
• With the growth of the body, the head, which
occupies approximately half of the body
length initially, gets reduced to about one-
quarter at birth