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End of 5
TH
week IUL
12
TH
week IUL End of 6
th

Week IUL
Beginning of 9
th

week
CRI TI CAL PERI OD
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The entire palate develops from
two primorida
, and


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Week 6:
A cut between the maxillary and
the mandibular prominences and
tipping the top of the head back
allows visualization of the
developing palate.
The secondary palatal shelves
are considered to be part of the
maxillary prominences.
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Week 6:
The medial nasal
prominences
merge in the
midline to smooth
the median furrow.

This fusion
produces a wedge-
shaped mass of
mesenchymal
tissue known as
the intermaxillary
segment.
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Week 6:

After the oronasal
membrane ruptures,
The intermaxillary
segment will form the
anterior part of the
palate, the primary
palate (circled).

This section is cut like
the last one (b/w
maxillary & mandibular
prominences)
1.
2.
3.
4.
5.
6.
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A higher magnification view of the
circled area illustrates the oronasal
membrane that is beginning to break
down.

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Week 7:
A parasagittal cut illustrates that the
oronasal membrane breaks down to
allow continuity between the nasal pit
and the common oral and nasal
cavities.
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Secondary Palatal
Shelves
Week 8:

A frontal cut
illustrates that the
tongue is initially
interposed
between the
secondary palatal
shelves.
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The two lateral maxillary palatal
shelves and the primary palate of
the frontonasal prominenceare
initially widely separated due to the
vertical orientation of the lateral
shelves on either side of the
tongue.
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Elevation of head and lower jaw
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Mechanism of palatal shelf elevation
*Intrinsic Force within the shelf (accumulation and hydration of hyaluronic
acid)
*Accumulation of Glycosaminoglycans
*EGF(epidermal growth factor) andTGF (transforming growth factor h3)
stimulate production of Hyluronan
*Increase in vascularity
*Contraction of elastic fibres or muscle fibres.
*Unequal division in the palatal and the oral epithelium
*Neurotransmitters like Serotonin
*Increase in MMP-3
*Upregulation of Vimentin expression
*Master controlling gene is FSP-1
(gene encoding a fibroblast-specific protein) ,
ssh
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Pressure differences between the nasal and
oral regions due to tongue muscle
contractions may account for the palatal
shelf elevation. This occurs at about 8
th
and
9
th
week p.c.. It is possible that the nerve
supply to tongue is sufficiently developed to
provide neuromuscular guidance to the
intricate activity of palatal elevation
followed by closure.
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Shelf elevation and fusion begin
a few days earlier in male than
in female embryos, possibly
accounting for sex differences
in the incidence of cleft palate.

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During palate closure, the mandible becomes
more prognathic and the vertical dimension of
the stomodeal chamber increases, but
maxillary width remains stable, allowing shelf
contact to occur.
Also, forward growth of Meckels cartilage
relocates the tongue more anteriorly,
concomitant with upper-facial
elevation.
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The transition from vertical to horizontal is completed within hours
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Week 9:
The palatal shelves
become positioned
above the tongue to
allow for fusion in the
midline.
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Week 9: Fusion begins
The secondary palatal shelves change their
contours towards a midpoint from which they
fuse anteriorly and posteriorly.
At this point, the nasal septum grows
downwardly from the fused medial nasal
processes.
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Medial Edge Epithelium. (M.E.E.)
During the initial stage of the fusion process, MEE cells form a midline
epithelial seam (MES) separating mesenchymes of the two apposing
shelves.

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For the complete fusion of the palate, the MEE
acts as a barrier:

Epithelium cells of MEE transforms into
connective tissue cells.

Epithelium undergoes necrosis. (not supported
as microscopic structure Doesnt show any
necrotic cells)

Epithelial cells migrate towards oral and nasal
cells.

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Release of MMP (Matrix
metalloproteinase) causes
disintegration of the cells and
allows the connective tissue to
mix up.

Balance between the MMP and
TIMMP (Tissue inhibiting MMP)

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The loss of epithelial continuity in the area
of the shelf contact was originally
described as a classic example of apoptosis
(programmed cell death).

Two other mechanisms may also play a role
in palatal shelf fusion.

Migration of the basal cells into the
mesenchyme and differentiation of these cells
into mesenchymal cells.

Cells near the periphery appear to migrate to the
nearest epithelial surface, and then differentiate
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Since the differentiation
patterns of MEE cells in the
cultured single palatal shelf is
similar to that observed during
palatal fusion (Mori et al. , 1994; Martnez-lvarez
et al. , 2000), it is clear that terminal
differentiation of MEE cells is
not necessarily dependent on
palatal shelf contact and
midline seam formation in vitro

Int. J. Dev. Biol. 48: 307-317 (2004)
TOSHIYA TAKIGAWA and KOHEI SHIOTA
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Week 10
Fusion of the palatal shelves with each other
and with the nasal septum separates the nasal
cavities from the oval cavity.
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Fusion of the three palatal
components initially produces a
flat unarched roof to the mouth.



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Ossification of the palate proceeds
during the 8th week post conception
from the spread of bone into the
mesenchyme of the fused lateral
palatal shelves and from trabeculae
appearing in the primary palate as
premaxillary centers, all derived
from the single primary ossification
centers of the maxillae.
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Posteriorly, the hard palate is
ossified by trabeculae
spreading from the single
primary ossification centers of
each of the palatine bones.

Most posterior part - no
ossification - soft palate


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Week 10
The four maxillary incisors develop within the
primary palate.
Fusion completes at week 12.
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Note: tongue has
been removed.
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Appears at 10 wk IU
Growth ceases b/w 1 - 2 yrs
But no synostosis till
adulthood
RME can be done
Obliteration starts in
adolesence but complete
fusion occurs by 30 yrs.

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Eruption of teeth Deepening of palatal
vault
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Musculature of palate
Tensor veli palatini 40 days 1
st
arch
Palatopharangeous 45 days
Levator veli palatini 8
th
week 2
nd
arch
Palatoglossus 9
th
week
Uvular muscle 11
th
week 2
nd
arch

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First to develop at 10th week IU.

Develop from middle meatus by
primary pneumatization in ecto-
ethmoidal cartilage

Secondary pneumatization in
ossifying maxilla starts at 5th
month IU.

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Post natal growth of
maxilla
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General features
Three dimensional growth of maxilla
Height (Vertical)
Width (Transverse)
Length (Ant-Post)
Theories of growth
Sutural
Cartilaginous
Functional matrix theory

Key factors in Nasomaxillary remodelling
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Primary displacement

Secondary displacement

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Reversal line
Directions of growth sequentially
undergo reversals

A reversal line showing the
crossover between resorptive and
depository growth fields seen in
microscope

Factors affecting reversal shape of
bone muscle attachments rotations
growth fields
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Post natal growth of maxilla
apposition resorption
MOSS
Transformation
Translation
SUTURES
Displacement
Surface remodeling
CRANIAL BASE MAXILLA
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Sutural
Nasal septum
Surface apposition and resorption on
periosteal and endosteal surfaces
Alveolar process
Spheno occipital synchondrosis
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Surface apposition
Sutural growth
Nasal septum growth
Spheno occipital synchondrosis
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In contrast to cranial base maxilla is
dominated by intra membranous ossification
Endochondral bone growth seen at the
ethmoid bone and nasal septum

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Surface apposition
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Growth according to
various theories
Sutural Theory (Weinman
&Sicher)

Cartilagenous Theory ( Scott)

Functional Matrix Theory
(Moss)
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Sutural Theory
Bone growth in various
maxillary sutures

Causes pushing apart of
bone

Resultant thrust on whole
maxilla in forward and
downward direction

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Shortcomings of sutural
theory
Not pressure related - Tension
adapted tissue.

No innate growth potential.

Crouzons syndrome
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Cartilagenous Theory

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Primary Pneumatization
Ethmoid air cells from the
middle and superior meatus and
sphenoethmoid recess invade
the ectethmoid nasal capsule
(primary pneumatization), from
the 4th month post conception.

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Secondary
Pneumatization
Secondary pneumatization
occurs between birth and 2
years as groups of 3 to 15 air
cells grow irregularly to form
the ethmoid labyrinth

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Vimentin is a member of the
intermediate filament family of
proteins. Intermediate filaments
are an important structural
feature of eukaryotic cells.
They, along with microtubules
and actin microfilaments, make
up the cytoskeleton
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Human fibroblast stromelysin (also called transin or
matrix metalloproteinase-3) is a proteoglycanase
closely related to collagenase (MMP1) with a wide
range of substrate specificities. It is a secreted
metalloprotease produced predominantly by
connective tissue cells. Together with other
metalloproteases, it can synergistically degrade
the major components of the extracellular matrix
(Sellers and Murphy, 1981). Stromelysin is capable
of degrading proteoglycan, fibronectin, laminin, and
type IV collagen, but not interstitial type I collagen.
matrix
metalloproteinase-3
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