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Journal of
Dental Research
http://jdr.sagepub.com/
The Time-Structure Relationship of Tooth Development in Human
Embryogenesis
C.H. Tonge
J DENT RES 1969 48: 745
DOI: 10.1177/00220345690480052301
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The Time-Structure Relationship of Tooth Development in
Human Embryogenesis
C. H. TONGE
Department of Oral Anatomy, University of Newcastle upon Tyne, Newcastle upon Tyne,
England
The sequence of appearance of the cytological and morphological features of oral
and tooth differentiation was assessed, relative to general embryological processes, in
Inhuan embryonic material. The phases
considered were as follows: potentiality (022 days); interaction (23-32 days); and specificity of individual structural formation (3248 days).
allocating specimens to Streeter ho-
rizons.'0-'2"7'35'38'39
(3) Recording menstrual age and Streeter
horizons.23
(4) Using various different technics
basing the age according to
crown rump measurement of
embryo. 14-16,18-2 0,24-26,3 2-34,36
(5) Measurements alone with no
for
the
the
ag-
ing.3,21,22,27-3'
Detailed information on the timing of human odontogenesis relative to other structural differentiations is necessary to apply
the results of animal in vitro studiesl-5 to
man. Human embryos have been described
before and during implantation, forming
endoderm, the embryonic disk, the primitive streak and its head process, and showing
neural grooves and neural crest migra-
The purpose of the present investigation
was to define, within the first 48 days after
ovulation. the sequence of appearance and
identification of the oral structures, indicating general embryological processes and
local features, such as innervation, ossification, myogenesis, oral epithelial differentiation, and the isolation and continued differentiation within a limited local environtions.6-9
ment of the early developing tooth.
Separate descriptions of different embryMaterials and Methods
onic collections have been recorded for
mouth development:10 early odontogeneA range of 31 human embryos (Table 1)
SiS :11,12 permanent-tooth germ formation;'3 was allocated38 to Streeter horizons XIIIthe morphogenesis of the dental arches;'4"15 XXIII, 27 to 48 days ovulation age. Serial
the development of taste buds;16 palatal sections at 8 micrometers (pm) of cold
morphogenesis;17-19 oral mucosa;20 its kera- neutral formalin, paraffin-embedded material
tinization21 and hemopoiesis;22 facial nerve23 were stained by various cellular and connecand muscle development;24 the relationship tive tissue stains. Wax-plate reconstructions
of trigeminal nerve fibers to tooth germ,25 were made of selected specimens. Comparioral mucosa, and cutaneous areas.26 Other son was made with published illustrarecent human developmental studies include tions.1-38 The photographs of the normal 19
observations on the motor end plate in specimens (Streeter horizons XVI-XXIII)
tongue musculature;27 a 34-mm sku1128 and in Kraus, Kitamura, and Latham39 were also
mandible;29 the tubotympanic recess;30 the studied.
remains of Meckel's cartilage;2' the tempoResults
romandibular joint;32,33 accessory thyroid
0-27 DAYS.-The literature has retissue;34 the third bronchial duct;35 and the
histogenesis of the bronchial cyst.36'37
corded6-9,38 a two-cell stage at 1½2 to 21/2
Methods employed for timing the se- days; a 12-cell morula at 3 days; and a 107cell blastocyst, of which eight are embryoquence of events include:
forming at 4 to 41/2 days, endoderm at 71/2
(1) Knowledge of the ovulation age.7-9
(2) Estimation of the ovulation age by days, an ectodermal plate at 91/2 days, and
745
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746
TONG E,
7 Dent Res Supplemnent to No. S
BLE
EMBRYO ALLOCATION TO STREETERt HORIZONS
Streeter
lorizoll
XIII
XIV
XV
XVI
XVII
XVIII
XIX
XX
XXI
XXiI
XXIII
Number of
olinbrvo s
C(row n -Rump
Range (nr m)
I
2
5.0
5.6- 7.0
11.0
11.0-12.0
12.0-15.0
15.0-21.0
18.0 19.0
3
3
5
4
3
2
2
5
20.0-20.6
22.824.0
25.0
28.0--31.4
O( vllatioln
\ge (days)
27- 29
28-30
31 32
32-24
34---36
36--38
38 -40
40 42
42 44
44--46
46--48
lay in contact. The epithelium lining the
roof of the pharynzgeal region was singlecell cuboidal; that lining the floor and lateral
walls was proliferative with marginal epithelial outgrowths. The first aortic artery
traversed the mandibular arch. It was endo-
thelially lined and contained nucleated blood
cells passing toward the epithelial surface
(Fig 1 ). Lingual swellings, tuberculunm
impar, and thyroid Outgrowth were identified. The atrial myocardium was two to
three-cells thick; the ventricular myocardium
showed trabeculation. and the endocardial
cushions of the atrioventricular valves were
outlined. The lower limb bud was smaller
but similar to the arm bud. No identifiable
tooth-bearing region nor salivary gland formation was present.
HORIZON xiv, 28-30 DAYS.-Lens disks
were invaginated and communicated by narrow pores with the surface. Arm buds projected as appendages from the body wall.
but no differentiated hand plates were seen.
Mandibular and hyoid arches marked surface elevations, with the third arch being
much smaller. Thyroid diverticulum wasS
still connected with the pharyngeal surface.
Rathke's pouch and pituitary were observed.
The trachea was separate from the esophagus. Primary bronchi and epithelial-lined
lung buds were formed. Bowman's capsule
was identified cephalically with the single
vesicles of the mesonephros caudally. Mesenchyme condensing around the notochord
and posterior nerve root ganglia and spinal
nerves were differentiating. The tissue, in
which the structures of the floor of the
an embryonic disk by 12 days. The presomite phase was completed with the primitive
streak at 15 days, its head (notochordal)
process at 18 days, and neural groove at 1 6
days. The notochord elongated cephalically;
early somites and the neural folds appeared
by 21 to 23 days. At 23 to 25 days the first
heart pulsations and a simple vascular plexiform arrangement of endothelium aided
fluid movement. Neural ectoderm was separating from skin ectoderm, early neurl
crest migrations occurred, and the anterior
neuropore was closing. The mandibular and
hyoid arches and 13 to 20 somites were
present. The buccopharyngeal membrane
had not ruptured, and pituitary formation
was commencing. The brain vesicles were
becoming defined, as were the fifth, seventh.
and eighth cranial nerves, with the ninth
and tenth less definite. Embryos between
25 to 27 days had 21 to 29 somites, arm
buds, three bronchial arches, partial closure
of the posterior neusropore, and epithelial
differentiation for the liver, lung, stomach.
and pancreas. Pharyngeal epithelial proliferations included the thyroid, parathyroid, and
thymic outgrowths. An adequate blood suIpply reached the liver, yolk sac, cranial
ganglia, bronchial arches, and the surface of
the central nervous system.
HORIZON XiiI, 27-29 DAYS. The nCuropores were closed; a retinal region bulged
backward into the l]umen of the optic
4s
o
evagination with no lens formation. The
m'
t)
otocyst opening on to the surface had
,'.
Aw,
thick epithelium, contrasted with the single
FIG
1.
The
floor
of
the
oral region in 5layer of flattened cells lining the skin. The
mm-crown-rump
embryo,
horizon
X1I1, 27-29
frontonasal process, mandibular, hyoid and
The first aortic arch artery traverses the
third arches, with the pericardium were days.
tissue, and numeroLus nucleated blood cells
identified together with three bronchial mem- can be seen in it and close to the epithelial
branes where skin and pharyngeal epithelial surface.
I'm~~~~~~~~~~~
4
E
a
'
'.
B
it
R:
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ff
Vol 48, 1969
HUMAN EMBRYOGENESIS RELATIVE TO ODONTOGENESIS
mouth form, had become defined by the
growth of the mandibular processes. The
lingual swellings and midline intermandibular sulcus were seen; the mandibular arch
was packed with mesenchymal cells laterally,
although these were less dense centrally. An
amorphous matrix packed the interstices between the irregular mesenchyma cells, which
had long slender processes. A potentially
odontogenic epithelium of the tall cuboidal
variety was well marked in the premaxillary
(primitive palate) and mandibular regions.
There was an ill-defined mesenchymal condensation beneath it. No salivary gland formation was observed but there was a
thickened epithelium in the maxillary-mandibular junctional area.
HORIZON XV, 31-32 DAYS.-The olfactory
pit was sufficiently invaginated for its edges
to be defined and the lateral nasal process
and primitive palate to be easily identified.
Lens vesicles were closed. Cranial ganglia of
trigeminal, facial, glossopharyngeal, and
vagus had formed. Trachea and esophagus
were contained in a common mesenchymal
condensation. The posterior part of the
tongue and adjacent posterior pharyngeal
wall were lined by a cuboidal epithelium arranged in several layers; the anterior part by
one or two cell layers. The thyroid diverticulum was losing its attachment to the lingual
pit. There was evidence of migration of the
occipital myotomes forming the tongue muscles. The orientation of the cells beneath
the epithelium suggested the direction of
the superior longitudinal muscle layer, although the presence of myoblasts was not
confirmed. The epithelium of the oral cavity
and the odontogenic area was similar to the
last horizon. No salivary glandular epithelium was identified, but a region later forming the mesenchymal bed of the submandibular gland was located.
HORIZON XVI, 3 2-34 DAYS-.Nasal placodes were directed laterally. The deepest
part of the olfactory pit was visible from
the side, together with separate medial and
lateral nasal processes. Auricular tubercles
were present. The handplate with the primary marginal vein was separate from the
arm and shoulder in which precartilage
condensations were observed. The surface
elevations of underlying somites and spinal
ganglia were restricted to the region caudal
to the arm bud. The ventricles were separating and the aorta and pulmonary trunk were
747
forming from the truncus arteriosis. The
trachea and primary bronchi lay in mesenchyma separate from that surrounding the
esophagus. The bronchial region, without
cartilage formation, was characterized by
the presence of recognizable cellular condensations related to nerve trunks. The
chorda tympani nerve was entering the mandibular arch; the mandibular nerve had a
cellular collection around it, the whole forming a nerve-ganglion mass giving rise to the
lingual nerve and submandibular ganglion.
Small blood vessels accompanied the nerves.
The facial nerve lay within the second arch
tissue.
The genioglossus and geniohyoid muscles
formed a common mass toward which the
hypoglossal nerve was passing. The central
region between the muscles of the two sides
was less cellular. A condensation beneath
the surface was probably associated with
the intrinsic musculature. In the most developed embryo allocated to this horizon
the mylohyoid muscle condensation was
identifiable. The thyroid gland freed from
the surface was located within the central
zone of less condensed cells. Rathke's pouch
was well developed. In the posterior pharyngeal wall, lined with two to three layers of
cuboidal cells, the underlying notochord was
surrounded by dense mesenchyma. The scalp
was covered by a single layer of cells. The
underlying mesenchyma was condensed beneath the developing forebrain and in the
region in which the facial muscles form. A
clearly defined odontogenic epithelium, comprising two to three layers of columnar
cells, could be traced over the premaxillary
and mandibular regions. The underlying
condensed and proliferating mesenchyma
showed a definite orientation relative to the
odontogenic epithelium (Fig 2).
HORIZON XVII, 34-36 DAYS.-An olfactory
region was recognizably different from the
respiratory region, and the vomeronasal
organ was differentiating. Primary palate and
primitive posterior nares were observed. The
maxillary processes were forming the earliest
shelves for the secondary palate. Precartilage
condensations for Meckel's cartilage, hyoid
bar, tracheal and laryngeal cartilages were
identified. Condensing perichondrium existed
around the limb cartilages. Early muscle
formation appeared in the walls of the
alimentary canal. Aortic and pulmonary
valves were present. In the floor of the
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748
F/ONGE
FIG 2. The premaxilla (A) and mandibular
area (B) in an 11.5-mm-crown-rump embryo,
horizon XVI, 32-34 days. In both areas odontogenic epitheliUm with underlying mesenchyma
becoming oriented relative to it can be observed. It is made up of coluimnar cells in contrast to the flat cuiboidal cells elsewhere.
J D7eONt Res.6 Supplement In No.
for the lower incisors being more pr1 onounced (Fig 3). The mylohyoid muscle
formed a complete floor to the mouth between the Meckelfs cartilages to the perichondrium to which it was attached. The
anterior belly of the digastric reinforced its
anterior part, and behind the posterior part
of the mylohyoid the submandibular gland
mesenchyma, now clear rlv delineated, conilt1
be observed (Fig 4). A well-marked condensation was appearing lateral to the
Meckel's cartilage and was the precursor of
mandibular development. The superficial
group of facial muscles was not separately
identifiable, with the exception of the orbicularis-oculi groUp. The posterior belly of the
digastric was visible. In the limbs, hyaline
cartilage, a perichondrium, and muscle
groups were observed. The development ol
the femur was the most complete.
HORIZON XIX, 38-40 DAYS. The vCstilbL-
mouth, the lingual and inferior dental nerves
together, the submandibular ganglion, and
the hypoglossal nerve were identified. The
epithelial bud of the submandibular gland
extended toward the mesenchymal condensation, which had not yet clearly defined
limitations. The geniohyoid was identified
separately from the genioglossus. The nerve
to the mylohyoid entered a premUscle condensation in which differentiating myoblasts
formed the mylohyoil. The more superficial
cells of this condensation may form the
anterior belly of the digastric muscle. Tooth
development is essentially similar to the
previous horizon.
HORIZON XVIII, 36-38 I)AYS.-The basic
external features of the face had become
established. The base of the skull in the
sphenoidal region was a. precartilaginous
mesenchymra in which the notochord had
lost its separate identity, although Rathke's
pouch had not disappeared. The epithelium
of the oral cavity was cuboidal, with one
or more layers of flattened cells upon its
surface. The anterior two-thirds of the
tongue was similar, the cells showing frequent evidence of mitosis; but no taste bud
formation had occurred. The cells on the
posterior third of the tongue were taller,
with a reduction in cell layers. Within the
odontogenic regions some specialized formation for individual teeth was occurring as
a result of the formation of well-marked
cellular clusters. Individual regions for the
incisor teeth could be demonstrated, those
Ar
* .t,*,
'V4 v .*
FIG; 3.- The Lipper (AI) and lower (B) inareas of cl '2-mm-crown rump ernbryo,
horizon XV111, .36-38 days, in which individl-iY1
centers are forming for the teeth within tile
odontogenic epithelium. The proliferating cells
are arranged in c1 asters, concentrically aroulL
the center.
cisor
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Vol 48, 1969
IIUANAN EMBRYOGENESIS RELATIVE TO ODONTOGENESIS
The floor of the mouth in a 16-mmembryo, horizon XVIII, 36-38
days. The submandibular ganglion and lingual
nerve (A); mesenchymal bed of the submandibular gland (B), in which the epithelial downgrowth is invaginating; and the mylohyoid
mUscle and nerve (C) can be observed.
FIG 4.
crown-rump
lar sulcus was forming in both jaws, the epithelial invagination into condensing mesenchyma was occurring in the identifiable
odontogenic regions, which were now recognizable for the incisor, canine, and firstmolar entities of both jaws. The epithelial
region for the lower second molar was
identified in one specimen allocated to this
horizon. There is some evidence of papillae
formation on the surface of the anterior twothirds of the tongue. Meckel's cartilages were
complete, and ossification in the mandibular region had commenced, the early osteoid being demonstrable. A mesenchymal
condensation for the elevator muscles and
associated mandibular ramus region was observed.
HORIZON xx, 40-42 DAYS.-The palatal
shelves of the maxillary processes lay alongside the tongue, the muscles of which had
myoblasts with single nuclei, and which oc-
749
cupied a large part of the common buccobasal cavity. The parotid outgrowth was a
solid mass of cells lying close to the condensation for the masseter muscle. The
inferior dental nerve lay in a gutter formed
by the developing mandible. There was evidence of maxillary ossification in the canine
and incisor regions. The dental lamina was
forming as the tooth buds, each having a
different shape and size, entered the mesenchyma from the odontogenic epithelial surface. In the interdental regions there was
little cell proliferation and almost no penetration into the mesenchyma. The limits of
the future gingival regions, both palatally or
lingually and on the vestibular aspect, could
be determined. The genial tubercles could be
identified with the attached geniohyoid and
genioglossus muscles.
HORIZON XXI, 42-44 DAYS.- The parotid
and submandibular outgrowths were tubular.
Bone was forming around Meckel's cartilage.
The temporalis, masseter, medial, and lateral
pterygoid muscles could be identified with
individual muscle fiber formation for the
mylohyoid and anterior belly of the digastric.
HORIZON xXII1, 44-46 DAYS. Well-marked
dental papilla with a dental follicle surrounding it were observed. There was increasing
emphasis on the separation of the lip, the
development of the vestibular sulcus, and
the formation of the dental lamina.
HORIZON XXIII, 46-48 DAYS. The membranous skull was forming; nasal meati and
spheno-ethmoidal recess lined by olfactory
epithelium was defined. Secondary palatal
shelf fusion was occurring, but no nasal
septal fusion was seen. Costal cartilages, ribs,
intercostal muscles, laryngeal muscles, and
vocal cords were identified. The muscles of
facial expression were separately demonstrated. Meckel's cartilage was being replaced by bone anteriorly Mylohyoid was
attached to a well-marked raphe anteriorly
and the hyoid bone posteriorly with a cleft
for blood vessels and lymphatics passing toward the developing submandibular lymphatic glands. The submandibular salivary
gland showed a branching canalization of its
duct system. Individual tooth germs with
restricted interdental regions, well-formed
dental laminae, and dental papillae contained within a dental follicle were observed.
The superficial part of the dental lamina
stained histologically and histochemically
like the oral mucosa and was nonodonto-
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TONGE
750
J Dent Res Supplement to No. 5
genic, the deeper part being similar to the
external dental epithelium.
Discussion
The literature is extensive concerning the
determination of embryonic age, but there
is no certain method for ascertaining it with
absolute accuracy. The work of Streeter,38
by establishing identifiable developmental
horizons linked to ovulation age, has become
the accepted basis for recording the sequence
of embryonic development. In considering
the significance of any particular embryonic
organization relative to mouth and tooth differentiation, the classical studies of Spemann40 point the way by indicating the
necessity of having ectoderm in contact with
mouth endoderm before tooth formation can
occur. Indeed, the endoderm seem to be the
more important, since only after induction
does the ectoderm become labeled as tooth
forming. Further differentiation proceeds as
an interdependence of ectoderm on the underlying mesenchyma. Studies in cell bi-
ology41 have shown that a chemical and
largely protein basis is involved in the complex mechanisms concerned with the progressive limitation of genetic potentiality
associated with the progressive cytodifferentiation and tissue organization that is necessary in the formation of separate organ
systems. This clearly adds to the knowledge
of the mode of action of organizers and is
a logical extension of the principles elaborated by Waddington.42
In applying the results of this investigation
to an assessment of the sequence of events
associated with the appearance and identification of oral structures, it seems reasonable
to divide the first 48 days after ovulation
into three phases: (1) potentiality (2) interaction, and (3) specificity (Table 2). Potentiality is essentially that period during
which the initial genetic totality of cells is
being limited as differentiation takes place.
This is the phase during which the embryonic disk is formed, the primitive streak and
notochord differentiate, while regionalization
TABLE 2
EMBRYONIC FORMATIONS 0-48 DAYS
Phase
Potentiality
112
3
4Y2
712
912
12
15
16
18
22
Interaction
23-25
25-27
27-29
28-30
31-32
Specificity
Observation
Days
32-34
34-36
36-38
38-40
40-42
42-44
44-46
46-48
Two-cell stage
Morula
Embryo-forming cells
Endoderm
Ectoderm + endoderm
Embryonic disk
Primitive streak
Neural groove
Notochord
Closure of neural tube with open neuropores, optic and otic vesicles,
7 somites
Neural crest migration; heart pulsations; 1st, 2nd bronchial arches;
pituitary; 5th, 7th, 8th nerves; 13-20 somites
Arm buds, 3 bronchial arches, liver, lung, stomach, pancreas, thyroid,
parathyroid and thymic growths
Neuropores closed, no lens, 3 bronchial arches and membranes, lingual
swellings, tuberculum impar
Trachea separate from esophagus, primary bronchi, lung buds, mandibular
arch packed with mesenchyma, primitive palatal process
Odontogenic epithelium; occipital myotomes for tongue; 5th, 7th, 9th,
10th nerve ganglia formed; lateral nasal process
Handplate, submandibular ganglion, lingual N, parotid gland, genioglossus
and geniohyoid muscles, 12th nerve
Secondary palatal shelves, precartilage bronchial bars, mylohyoid mass,
submandibular gland
Face formed, incisor tooth regions, oral floor complete
Vestibular sulcus, canine and first molar areas, mandibular ossification,
mandibular ramus condensation with elevator muscles
Maxillary ossification, genial tubercles, dental laminas
Tubular outgrowths for parotid and submandibular glands
Dental papillae with dental follicle formation
Secondary palatal fusion, facial muscles, individual tooth germs, salivary
gland ducts branching
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Vol 48, 1969
HUMAN EMBRYOGENESIS RELATIVE TO ODONTOGENESIS
751
Germs in a Chemically Defined Proteinoccurs, and the neural plates and tubes show
Free Medium, Arch Oral Biol 9:27-30,
morphological differences at the various
1964.
axial levels. Cranially, a potential brain
PouRTois, M.: Contribution a l'Ptude des
forms, optic and otic outgrowths arise, and 3. Burgeons
Dentaires Chez la Souris: I.
early somites develop. Potentiality in man
Periodes d'Induction et de Morphodiflasts for 22 to 23 days and then merges with
ferenciation, Arch Biol (Paris et Lietge)
interaction. Interaction, extending from 23
72:17-95, 1961.
to 32 days, is essentially the phase when an 4. PouRTois, M.: Comportement en Culture
inductive relationship exists between one
in vitro des Abauches Dentaires de Rongeurs Prdelevees aux Stades de Predifferenciagroup of differentiated cells and other groups
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1964.
occur. Innumerable mechanisms belong to
L.C.: The Epigenetics of Early
this category and include the formation of 5. DRYBURGH,
in the Mouse, J Dent
Tooth
Development
the lens from the surface ectoderm by means
Res 46:6 (suppl) 1264, 1967.
of the inductive capacity of the optic cup. 6. HERTIG,
A.T., and ROCK, J. Implantation
Similarly, a mouth forms. The interaction of
and Early Development of Human Ovum,
cell layers continues until the completion of
Amer J Obstet Gynec 61A (suppl); 8-14,
induction results in the labeling of cells to
1951.
form specific structures without the capacity 7. HERTIG, A.T., and ROCK, J. Two Human
Ova of the Pre-villous Stage, Having and
for dedifferentiation. Specificity, from 32 to
Ovulation Age of about Seven and Nine
48 days, is the phase during which individual
Days Respectively, Contr Embryol Carneg
structures are formed independently of other
(No. 200) 31:65-84, 1945.
structures. Bone develops, teeth form, sal- 8. Inst
HERTIG, A.T.; ROCK, J.; and ADAMS, E.C.
ivary glands differentiate, and all have their
A Description of 34 Human Ova within
own precisely defined territories. The tooth
the First 17 Days of Development, Amer
germ has a dental follicle43 to maintain its
J Anat 98:435-493, 1956.
histological and histochemical independence 9. BARTELMEZ, G.W., and DEKABAN, A.S. The
Early Development of the Human Brain,
of other structures.
Contr Embryol Carneg Inst (No. 621) 37:
Summary
13-32, 1962.
A study of the first 48 days after ovulation 10. TONGE, C.H. Basic Aspects of Mouth Development, Proc Roy Soc Med 50:185-190,
has been made on human material, indicat1957.
ing the general embryological processes and 11. TONGE,
C.H. Advances in Dental Embryof
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the regional features
ology, Int Dent J 16:328-349, 1966.
ferentiation. The sequence of appearance of 12. TONGE, C.H. Identification of Cell Patterns
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in Human Tooth Differentiation J Dent
differentiations has been arranged in phases:
Res 46:5 (suppl) 876-878, 1967.
of potentiality, 0 to 22 days; of interaction, 13. OOE, T. A Study of the Ontogenetic Origin
of Human Permanent Tooth Germs,
22 to 32 days; and of specificity of individOkajimas Fol Anat Jap 40:429-437, 1965.
ual formation, 32 to 48 days. In the case of 14. Buim,
A.R., and LILLIE, J.H. A Catenary
31 human embryos allocated to Streeter
Analysis of the Maxillary Dental Arch durHorizons XIII-XXIII, 27 to 48 days, deing Human Embryogenesis, Anat Rec 154:
scriptions of each stage have been given
13-20, 1966.
with particular emphasis on oral and tooth 15. BURDI, A.R. Morphogenesis of Mandibular
Dental Arch Shape in Human Embryos,
differentiation. In each horizon reference
J Dent Res 47:50-58, 1968.
has been made to the major general developBRADLEY, R.M., and STERN, I.B. The Demental processes taking place at the same 16. velopment
of the Human Taste Bud during
time.
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The author thanks D. Golding for preparing the
illustrations and E. Breese for secretarial assistance.
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