The response of embryonic mouse dental epithelium and mesoderm to tissues of ectopic origin was examined. Isolated molar or incisor mesoderm was confronted with epithelium isolated from the plantar surface of the embryonic mouse foot plate or from the snout.

Harmoniously structured teeth were formed from the foot epithelium and incisor or molar mesoderm. These data are interpreted as an unequivocal demonstration of the inductive role of the dental mesenchyme.

Teeth were absent in confrontations of dental mesenchyme and snout epithelium. The presence of hair follicles in these explants is described and discussed with reference to other integumental epithelio-mesenchymal interactions.

Dental epithelium forms keratinizing surface-like epithelium and invading bands of epithelium in association with foot mesoderm; definitive structures are not formed.

On the other hand, when incisor or molar epithelium is associated with snout mesoderm, hair follicles are seen in addition to keratinizing surface-like epithelial configurations.

The roles of the epithelial and mesenchymal tissues and the nature of epithelio-mesenchymal interactions in the developing mouse integument are discussed.

Previous studies of tooth development have provided a number of important conclusions. (1) Both epithelium and mesenchyme must be present if tooth development is to proceed (Huggins, McCarroll & Dahlberg, 1934; Koch, 1967; Kollar & Baird, 1969). (2) The epithelium and mesoderm will develop typical matrices if physically separated by Millipore filters (Koch, 1967). (3) The structural specificity for the shape of the tooth germ resides in the mesoderm; typical incisiform and molariform patterns of cytodifferentiation are directed by the mesoderm (Kollar & Baird, 1969, 1970a, b). (4) The enamel organs from embryonic mice (Kollar & Baird, 1970a) and rabbits (Glasstone, 1952; Slavkin & Bavetta, 1968) remain plastic and will regulate far into the developmental period. (5) The lip-furrow epithelium, an epithelium temporally and spatially related to the incisor enamel organ, is able to regulate into harmonious tooth germs in the presence of incisor or molar mesoderm. Thus, the dental papilla can elicit new developmental expressions from the lip-furrow epithelium. These data imply an inductive interaction between the epithelium and the dental papilla (Kollar & Baird, 1970a).

These conclusions indicate that tooth development is the product of an epithelio-mesenchymal tissue interaction similar to interactions described for many other structures. However, an unequivocal demonstration that dental papillae induce tooth germs has been lacking.

This investigation describes experiments in which dental papillae from embryonic mice are associated with epithelium from embryonic snout and foot plate (plantar surface). The dental papillae induce recognizable tooth structures in the plantar surface epithelium from the foot plates of embryonic mice; matrix synthesis is induced in this surface epithelium. In addition, the previously described versatile developmental performance of the enamel organ (Kollar & Baird, 1970a) is confirmed and is extended to include the ability of the enamel epithelium to reorganize into0 surface epithelium and hair follicles when snout mesoderm is present.

Tissue sources

Molar and incisor tooth germs, snout skin (upper lip) containing the mystacial vibrissae primordia, and hairless plantar surface of posterior foot plates were dissected from embryonic C57/10 mouse embryos. Embryonic stages, spanning 12–16 days of gestation, were determined by the appearance of a vaginal plug and confirmed by the staging criteria of Grüneberg (1943).

Molar and incisor tooth germs from the mandibles of 14-and 16-day-old embryonic mice were used in this investigation. The in vivo and in vitro development of these tooth germs have been repeatedly described (Cohn, 1957; Hay, 1961; Glasstone, 1967; Kollar & Baird, 1968, 1969, 1970a). The reader should consult these papers.

The structure and development of mystacial vibrissae follicles (Davidson & Hardy, 1952; Hardy, 1949, 1951, 1968; Kollar, 1966) as well as the response of these follicles in tissue culture (Hardy, 1968; Kollar, 1966) have been described in detail. At 12 and 13 days of embryonic development, the upper lip contains a number of mystacial follicle primordia. The epithelium thickens to form placodes in association with mesodermal condensations. The epithelium continues to invade the mesoderm during subsequent days of development and eventually gives rise to hair follicles with keratinizing hair shafts. The mesodermal condensations are incorporated into the epithelial follicles as dermal papillae.

The plantar surfaces of posterior foot plates of 14-and 15-day-old embryos were chosen because this epithelium is hairless, and, at this developmental period, the mesodermal condensations associated with foot pads are beginning to develop. The dissection of this integumental site was performed so that only central portions of the plantar surfaces were excised. The tissue was trimmed so that contaminating skin containing hair follicle primordia was excluded.

Tissue separation and recombination

Trypsinization was accomplished by incubating excised tissue fragments with a 1% solution of trypsin (Bacto-Difco, 1:250) in Tyrode’s solution at 4°C for 1–2 h. The 12-day snout skin required 1 h of incubation; 16-day incisor germs required a minimum of 2 h incubation. This procedure is described in detail elsewhere (Kollar & Baird, 1969). The epithelial and mesodermal components separate at the basement membrane and can be handled as uncontaminated sheets of epithelium and mesoderm (Kollar, 1966; Kollar, 1970; Kollar & Baird, 1969, 1970a).

The isolated components were recombined as control and experimental combinations. The ability of the isolated tooth components to develop in culture and to produce type specific structures has already been described (Kollar & Baird, 1968, 1969). Control recombinants of snout epithelium (SE1213) and snout mesoderm (SM1213) as well as the control combinations of foot epithelium (FE1415) associated with its homologous foot mesoderm (FM1415) were reconstructed. These data are described elsewhere (Kollar, 1970).

Culture methods

The isolated tissue fragments were stored in a solution of foetal bovine serum and Tyrode (1:1, v/v) and were transferred to Falcon organ culture dishes containing 1 ml of Eagle’s basal medium containing 10% foetal bovine serum, 1% glutamine, 0·4% agar and 50 units/ml each of penicillin and streptomycin. The explants were incubated at 37°C in a humidified 5% CO2– 95% air-gas mixture and were allowed to cohere for 1 or 2 days on this medium.

When the explants had re-established a stable junction between the epithelium and mesoderm and could be transferred safely, they were grafted into the anterior chambers of homologous mice eyes. The grafted explants were allowed to grow for 1–2 weeks before harvesting.

Histology

The explants were fixed in Zenker’s acetic acid and decalcified with Versene (Schmidt, 1956). The tissue was paraffin-embedded, serially sectioned at 7μ and stained with hematoxylin and eosin (H and E) or Masson’s trichrome (MT).

Recombinations of dental mesoderm and foreign epithelium

(1) Dental mesenchyme combined with foot epithelium

The plantar surface of the posterior foot plate does not produce structurally complex epithelial adnexa. Thus, this set of experiments provided a crucial test of the inductive capabilities of the dental mesenchyme. The foot epithelium consistently produced surface epithelium characterized by extensive surface keratinization. The presence of tooth structures in these explants provided an unequivocal and dramatic demonstration of the inductive properties of the mesenchyme and the developmental plasticity of the epithelium.

When 15-day-old molar mesoderm was confronted with foot epithelium from 15-day-old embryos (MM15FE15) and allowed to grow in the eye for 2 weeks unmistakable teeth were produced (Fig. 1A–C). Similarly, when younger tissue components were combined (IM14FE14) tooth structures were recovered after 2 weeks of growth (Fig. 1D).

Figure 1

Scale line represents 50μ throughout except Fig. 1E.

(A) An harmonious tooth developing after 2 weeks in the anterior chamber from an explant of molar mesoderm and plantar surface foot epithelium (MM15FE15) from a 15-day-old embryo. Note the keratinizing epithelium (A) in close association with the tooth germ. MT. × 300. (B)A tooth-germ construction formed after 2 weeks in the anterior chamber. This graft was composed of molar mesenchyme and foot epithelium (MM15FE15) from a 15-day-old embryo. H and E. × 600.

(C)An harmonious tooth germ contiguous with a heavily keratinizing epithelium (k). This explant (MM15FE15) was grown in the anterior chamber for two weeks. MT. × 300.

(D)A tooth primordium developing in an explant (IM14FE14) after 2 weeks in the anterior chamber. Note the keratinizing epithelium (A) and an additional area suggestive of a tissue interaction (z). H and E. × 300.

(E)Integumental adnexa developing in a graft of dental mesenchyme and snout epithelium (IM14SE12) 2 weeks after explantation. Note the surface-like epithelium (se), the hair follicle with papilla (p) and keratinizing hair shaft (ks), and the sebaceous gland (sg). H and E. × 1000. Scale line = 15μ.

(F)Hair follicles developing in an explant of molar mesenchyme and snout epithelium (MM14SE12) after 1 week in culture. MT. × 750.

Figure 1

Scale line represents 50μ throughout except Fig. 1E.

(A) An harmonious tooth developing after 2 weeks in the anterior chamber from an explant of molar mesoderm and plantar surface foot epithelium (MM15FE15) from a 15-day-old embryo. Note the keratinizing epithelium (A) in close association with the tooth germ. MT. × 300. (B)A tooth-germ construction formed after 2 weeks in the anterior chamber. This graft was composed of molar mesenchyme and foot epithelium (MM15FE15) from a 15-day-old embryo. H and E. × 600.

(C)An harmonious tooth germ contiguous with a heavily keratinizing epithelium (k). This explant (MM15FE15) was grown in the anterior chamber for two weeks. MT. × 300.

(D)A tooth primordium developing in an explant (IM14FE14) after 2 weeks in the anterior chamber. Note the keratinizing epithelium (A) and an additional area suggestive of a tissue interaction (z). H and E. × 300.

(E)Integumental adnexa developing in a graft of dental mesenchyme and snout epithelium (IM14SE12) 2 weeks after explantation. Note the surface-like epithelium (se), the hair follicle with papilla (p) and keratinizing hair shaft (ks), and the sebaceous gland (sg). H and E. × 1000. Scale line = 15μ.

(F)Hair follicles developing in an explant of molar mesenchyme and snout epithelium (MM14SE12) after 1 week in culture. MT. × 750.

The tooth structures could be serially traced to the heavily keratinizing surface-like epithelial cysts and did not occur in isolation from the grafted epithelium. The deposition of matrix and the formation of dentin and enamel were harmoniously structured.

(2) Dental mesenchyme combined with snout epithelium

The development of snout epithelium confronted by dental mesenchyme was restricted to a more characteristic surface-like epithelial pattern. Stratified keratinizing epithelium and hair follicles were present in these grafts (Fig. 1E, F). Sebaceous glands were associated with the hair follicles. Because the presence of hair follicles in grafts composed of snout epithelium and dental mesenchyme were unexpected and of unusual interest, these experiments were repeated. The dental mesenchyme was severely trimmed in order to ensure that no other mandibular mesenchyme was present except the papilla and a narrow strip of surrounding mesenchyme. These experiments confirmed our earlier finding; hair follicles were present in these explants as well.

Recombinations of dental epithelium and foreign mesenchyme

(1) Dental epithelium combined with foot mesenchyme

The dental epithelium developed surface-like epithelial sheets; stratification and heavy keratinization were present. In addition, the basal layer of these epithelial sheets underwent extensive downgrowths into the foreign foot mesoderm (Fig. 2A, B). The pattern of collagen deposition was of interest in these grafts. The invading epithelium appeared to be walled off by heavy collagen deposition around the invading epithelium (Fig. 2C, D).

Figure 2

(A) This explant consists of molar epithelium and foot mesoderm and displays the extensive and random invasion of the mesoderm by dental epithelium. MT. × 750.

(B) Incisor enamel organ epithelium invades the foot mesoderm incorporating small clusters of mesodermal cells. MT. × 750.

(C) Heavy deposition of collagen (c) at the interface between incisor epithelium and foot mesoderm. MT. × 750.

(D) Collagen deposition (c) at the interface between molar epithelium and foot mesoderm. MT. × 500.

(E) An enamel organ-like epithelial configuration. Note the surface epithelium (se), the stellate reticulum-like (sr) epithelium and the overall shape of the epithelium. Epithelial proliferation can be seen budding from the enamel organ-like structure. This explant (ME15FM15) was grown for 2 weeks. MT. × 750.

Figure 2

(A) This explant consists of molar epithelium and foot mesoderm and displays the extensive and random invasion of the mesoderm by dental epithelium. MT. × 750.

(B) Incisor enamel organ epithelium invades the foot mesoderm incorporating small clusters of mesodermal cells. MT. × 750.

(C) Heavy deposition of collagen (c) at the interface between incisor epithelium and foot mesoderm. MT. × 750.

(D) Collagen deposition (c) at the interface between molar epithelium and foot mesoderm. MT. × 500.

(E) An enamel organ-like epithelial configuration. Note the surface epithelium (se), the stellate reticulum-like (sr) epithelium and the overall shape of the epithelium. Epithelial proliferation can be seen budding from the enamel organ-like structure. This explant (ME15FM15) was grown for 2 weeks. MT. × 750.

Several grafts provided insights into the source of the epithelial proliferation (Fig. 2C, E). When the plane of section was favorable, it was possible to trace the epithelial downgrowths serially to a section that appeared to be the original grafted enamel organ. For example, extensive epithelial proliferation appeared to originate from a tissue configuration similar to the enamel organ (Fig. 2E). Note that in the enamel organ-like configuration the cellular pattern includes a stellate reticulum. Similar observations were made when the incisor enamel organ (IE15FM15) was the source of the epithelium confronted by ectopic foot mesoderm (Fig. 2C).

Of unusual interest in these observations was the source of the proliferation from these enamel organ-like tissue patterns. The proliferation was most extensive from the outer enamel epithelium. Similar proliferations were seen along the inner enamel epithelium, but they were not as extensive as those apparently derived from the outer enamel epithelium.

(2) Dental epithelium combined with snout skin mesenchyme

The dental epithelium confronted with snout mesenchyme behaved in a fashion similar to its response to foot mesenchyme. Incisor or molar enamel organ epithelium from 14-and 15-day embryonic tooth germs displayed remarkable proliferative and invasive properties when associated with mesenchyme from 12-or 13-day-old embryonic snout skin. The dental epithelium produced keratinizing surface-like epithelium and deeply invaginating tongues of epithelium. The pattern of epithelial invasion into this ectopic mesenchyme resembled abortive enamel organ formations (Fig. 3A–C). At no time, however, did the dental epithelium or the snout mesenchyme suggest cellular

Figure 3

(A) This explant (ME15SM12) demonstrates the invasion of the molar epithelium into snout mesoderm. MT. × 625.

(B) Incisor epithelium incorporating snout mesoderm in an explant (IE14SM12) grown for 2 weeks. H and E. × 625.

(C) Incisor epithelium invading snout mesoderm (IE14SM12) in a fashion reminiscent of an enamel organ. H and E. × 750.

(D) Hair follicles and surface-like keratinizing epithelium derived from an explant of incisor epithelium and snout mesoderm (IE14SM12). H and E. × 300.

(E) An aberrant hair follicle developing in an explant (ME15SM12) composed of molar epithelium and snout mesoderm. Note the papilla (p) and keratinizing hair shaft (ks). H and E. × 750.

(F) A detail from Fig. E demonstrating the keratinized hair shaft. H and E. × 2800.

Figure 3

(A) This explant (ME15SM12) demonstrates the invasion of the molar epithelium into snout mesoderm. MT. × 625.

(B) Incisor epithelium incorporating snout mesoderm in an explant (IE14SM12) grown for 2 weeks. H and E. × 625.

(C) Incisor epithelium invading snout mesoderm (IE14SM12) in a fashion reminiscent of an enamel organ. H and E. × 750.

(D) Hair follicles and surface-like keratinizing epithelium derived from an explant of incisor epithelium and snout mesoderm (IE14SM12). H and E. × 300.

(E) An aberrant hair follicle developing in an explant (ME15SM12) composed of molar epithelium and snout mesoderm. Note the papilla (p) and keratinizing hair shaft (ks). H and E. × 750.

(F) A detail from Fig. E demonstrating the keratinized hair shaft. H and E. × 2800.

patterns typical of the inner enamel organ or an odontoblast layer of the mesenchyme; tooth structures were never seen in these explants. However, hair follicles were observed (Fig. 3D–F). The follicles were both pelage-and vibrissal-like. Occasionally, the follicle structure appeared aberrant, but, even in these cases, keratinizing hair shafts were present (Fig. 3E, F). In addition to the hair follicles, occasional small clusters of sebaceous glands were observed.

Induction by the dental papilla

The murine dental papilla elicits new developmental expressions from ectopic embryonic mouse epithelium. The deposition of dentin and enamel matrices in histotypic patterns clearly recognizable as tooth constructions indicates that the dental papillae act inductively during the ontogeny of teeth. Thus, these data provide a stringent test in that an unrelated non-dental epithelium in the presence of mesodermal tissue produces structural equivalents of the epithelium homologous to the inducing mesoderm. These data extend the observations of Lillie & Wang (1941, 1944), Wang (1943), Cairns & Saunders (1954), Gomot (1958), Rawles (1963), Sengel (1964), and others who have demonstrated the inductive nature of the local mesodermal components in the integument. Indeed, studies of epithelio-mesenchymal interactions in general confirm the notion that the mesodermal component is necessary for the induction and maintenance of ectodermal or endodermal structures during the early stages of development (see Wessells (1967), Grobstein (1967) and McLoughlin (1968) for reviews of the properties of epithelio-mesenchymal interactions in embryonic systems).

These data confirm our earlier data (Kollar & Baird, 1970 a) which showed that a more closely related epithelium, lip-furrow epithelium, can participate with the dental mesoderm to produce perfectly harmonious teeth. It is of interest that the structural harmony of the tooth germs induced in the lip-furrow epithelium is often more obvious than that produced in the foot epithelium. There is no doubt, however, that tooth structures are produced from the ectopic surface epithelium of the foot plate, although dental constructions easily scored as incisiform or molariform are less obvious in these latter experimental teeth. None the less, the production of dentin and enamel matrices in normal configurations, cytodifferentiation of the epithelium into a basal layer of cells with tall columnar cells that undergo a reversal in nuclear polarity, and specialized secretory activity are compelling demonstrations of mesodermal induction in interacting embryonic systems.

In contrast, the absence of tooth structures in experimental confrontations consisting of dental mesoderm and snout epithelium requires cautious interpretation. Despite the optimal culture conditions afforded by the intraocular site, the snout epithelium remained refractory to the inductive influence of the dental mesoderm. Certainly, the data of Rawles (1963) that clearly establish the importance of tissue age and the establishment of developmental stability in the epithelium must be considered here. It may be inferred from the present data that snout epithelium at 12 and 13 days of gestation has already stabilized and cannot respond to the inductive activity of dental mesoderm. Clearly, these negative data do not diminish the impact of the demonstration of the inductive role of dental mesoderm; rather, this series of experiments suggests that snoutskin epithelium must be examined at earlier ages.

In addition, this series of experiments can be viewed as an additional control for other combinations of dental mesoderm and ectopic epithelium. Since the dental mesoderm from a single litter was combined with snout and foot epithelium, the ectopic teeth formed by the foot epithelium cannot be the result of random contamination of the dental mesoderm with dental epithelial fragments. The complete absence of tooth structures or developing fragments of contaminating dental epithelia in the snout epithelium-dental mesoderm confrontations provides additional confirmation of the effectiveness and reliability of tissue separations after tryptic digestion.

The development of hair follicles in those explants composed of snout epithelium and dental mesenchyme provides further insights into the developmental performance of these two tissues. The persistence of hair follicles in carefully controlled experiments that excluded mandibular mesenchyme with potential hair-follicle-inducing qualities and the absence of hair follicles in other combinations of dental mesenchyme with homologous or heterologous epithelia confirm the view that snout epithelium and dental mesenchyme can participate in hair follicle development. At first view these data appear contradictory; however, these data are supported by similar observations in developing chick skin.

Rawles (1963) demonstrated that in the closely related avian feather-bearing dorsal skin and scaled metatarsal skin, developmentally advanced and stabilized back skin produces typical feathers when confronted with mesoderm from the scale-bearing mesoderm from the metatarsal region. In contrast, metatarsal mesoderm induces scales in younger feather-producing back skin. These data lead to the conclusion that a stabilized epithelium can produce type-specific structures when associated with an ectopic but related mesoderm.

The similarities between the snout hair follicle and dental structures must be considered in this context. The developmental origins of the snout and mandibular mesenchyme from the cranial neural crest, the similar trigeminal innervation to vibrissae follicles and teeth, and the anatomically similar developmental sequence in the initial development of the primordia of these dissimilar structures suggest that the phenomenon reported here may be similar to that described in avian skin. Thus, if 12-and 13-day-old embryonic snout epithelium has indeed stabilized and lost its regulative capabilities, the response of this epithelium to dental mesenchyme would be to produce type specific structures: hair follicles. This view must await confirmation from the response of 11-day snout epithelium confronted by dental mesenchyme. Younger, and therefore more plastic, epithelium should respond in predictable fashion; in the presence of dental mesenchyme, the more labile epithelium should produce dental structures.

These data demonstrate the inductive and supportive qualities of the mesenchyme in developing integumental systems and, once again, emphasize the importance of examining the temporal and spatial parameters that influence epithelio-mesenchymal interactions.

The response of the dental epithelium to foreign mesoderm

The dental epithelium does not produce recognizable structures when associated with foot mesoderm. Instead, the epithelium invades the mesenchyme and proliferates as crenulated epithelial bands. The observation that the epithelial proliferation originates, in part, from the outer epithelium of the enamel organ supports the view that this epithelium retains the properties of the stratum germinativum, and adds further support to the notion that during reconstruction of harmonious teeth from fragments of the enamel organ (Kollar & Baird, 1970 a, b) or in heterologous combinations of dental mesenchyme and enamel organs (Kollar & Baird, 1969) the outer enamel epithelium may contribute to the reorganization of the explanted dental epithelium.

The dental epithelium can participate in hair-shaft production when confronted by snout mesoderm containing the mystacial vibrissae dermal condensations. This ability of the dental epithelium to organize into new histotypic patterns, to suppress enamel matrix synthesis, and, instead, to produce organized keratinizing hair shafts and sebaceous glands, corroborates the inductive role of the vibrissae dermal condensations (Kollar, 1966, 1970) and the plasticity of the enamel organ epithelium. Our previous findings (Kollar & Baird, 1970 a) that the enamel organs of incisor germs from 16-day-old embryos can reconstruct complete tooth germs and keratinizing surface epithelia are supported by these new observations of regulative ability in the dental epithelium.

The pattern of epithelial invasion into an ectopic mesoderm also provides some insight into the nature of the interactions between the epithelium and the mesoderm. In those cases in which the dental epithelium is confronted with snout mesoderm the topography of the epithelium resembles an enamel organ rather than the basal layer of surface epithelium with follicle adnexa. The epithelium invades the mesoderm as crenulated tongues of epithelium incorporating mesodermal cells into the invaginations of the epithelium. This pattern of epithelial invasion is suggestive of the invasion pattern of the enamel organ. Often these structures were induced to form keratinizing hair shafts and sebaceous glands. Although some of these tissue configurations are not normal hair follicles, many other follicle structures are harmonious in all respects. Similarly, the dental epithelium invades the mesoderm of the foot plate in a fashion reminiscent of the enamel organ.

These data suggest that the invasiveness of the epithelium in relation to the mesoderm may be determined, in part, by inherent properties of the epithelium. On the other hand, the random nature of the epithelial invasion in these heterologous combinations suggests that the usual incisiform, molariform and follicle patterns are stabilized by some properties of homologous or closely related mesoderm. Thus, appropriate structural relationships are established by an interplay between the invasive properties of the epithelium and the modeling properties of the local inductive mesoderm. The depth of epithelial invasion, the definitive shape of the invading epithelium, and the spatial relationship of the epithelium to the inductive papilla appear to be determined by the mesoderm.

The data discussed here suggest that, as suspected, the development of teeth is the result of an epithelio-mesenchymal interaction not unlike many other developing systems in the avian and mammalian embryo. Once again, the lack of information concerning the processes involved in the inductive event is the most intriguing aspect of this problem.

Interactions tissulaires des germes dentaires de Souris

II Le rôle inducteur de la papille dentaire

La réponse de l’épithélium dentaire de l’embryon de Souris ainsi que du mésoderme à l’égard de tissus d’origine ectopique a été examinée. Du mésoderme molaire ou incisif isolé a été combiné à de l’épithélium isolé de la surface de la plaque plantaire d’embryon de souris ou à partir du museau.

Des dents harmonieusement constituées ont été formées à partir de l’épithélium de la patte combiné à du mésoderme incisif ou molaire. Ces résultats sont interprétés comme une démonstration non équivoque du rôle inducteur du mésenchyme dentaire.

Des dents ne se sont pas formées à la suite de la combinaison de mésoderme dentaire et de l’épithélium du museau. La présence de follicule pileux dans ces explants est décrite et discutée en relation avec les autres interactions épithélium-mésenchyme.

L’épithélium dentaire forme un épithélium à kératinisation de surface et des travées épithéliales profondes en réponse à la combinaison avec le mésoderme du pied; des structures définies ne sont pas formées.

Par ailleurs, lorsque l’épithélium incisif ou molaire est associé à du mésoderme du museau, on voit des follicules pileux s’ajouter aux formations épithéliales kératinisées en surface.

Les rôles des tissus épithéliaux et mésenchymateux et la nature des interactions épithélium-mésenchyme dans le développement du tégument de la souris sont discutés.

The authors wish to thank Dr Benson E. Ginsburg who generously made available his animal colony and animal care facilities. This research was supported by a grant from the American Cancer Society (ACS-IN-41-H). Finally, we wish to thank the Inland Steel-Ryerson Foundation for a Faculty Fellowship to E.J.K.

Cairns
,
J. M.
&
Saunders
,
J. W.
, Jr
. (
1954
),
The influence of embryonic mesoderm on the regional specification of epidermal derivatives in the chick
.
J. exp. Zool
.
127
,
221
248
.
Cohn
,
S. A.
(
1957
).
Development of molar teeth in the albino mouse
.
Am. J. Anat
.
101
,
295
320
.
Davidson
,
P.
&
Hardy
,
M. H.
(
1952
).
The development of mouse vibrissae in vivo and in vitro
.
J. Anat
.
86
,
342
356
.
Glasstone
,
S.
(
1952
).
The development of halved tooth germs; a study in experimental embryology
.
J. Anat
.
86
,
12
15
.
Glasstone
,
S.
(
1967
).
Morphodifferentiation of teeth in embryonic mandibular segments in tissue culture
.
J. dent. Res
.
46
,
611
614
.
Gomot
,
L.
(
1958
).
Interaction ectoderme-mésoderme dans la formation des invaginations uropygiennes des Oiseaux
.
J. Embryol. exp. Morph
.
6
,
162
170
.
Grobstein
,
C.
(
1967
).
Mechanisms of organogenetic tissue interaction
.
Natn. Cancer Inst. Monogr. no
.
26
,
279
299
.
Grüneberg
,
H.
(
1943
).
The development of some external features in mouse embryos
.
J. Hered
.
34
,
89
92
.
Hardy
,
M. H.
(
1949
).
The development of mouse hair in vitro with some observations on pigmentation
.
J. Anat
.
83
,
364
384
.
Hardy
,
M. H.
(
1951
).
The development of pelage hairs and vibrissae from skin in tissue culture
.
Ann. N. Y. Acad. Sci
.
53
,
546
551
.
Hardy
,
M. H.
(
1968
).
Glandular metaplasia of hair follicles and other responses to vitamin A excess in cultures of rodent skin
.
J. Embryol. exp. Morph
.
19
,
157
180
.
Hay
,
M. F.
(
1961
).
The development in vivo and in vitro of the lower incisor and molars of the mouse
.
Archs oral Biol
.
3
,
86
109
.
Huggins
,
C. B.
,
McCarroll
,
H. R.
&
Dahlberg
,
A. A.
(
1934
).
Transplantation of tooth germ elements and the experimental heterotopic formation of dentin and enamel
.
J. exp. Med
.
60
,
199
210
.
Koch
,
W. E.
(
1967
).
In vitro differentiation of tooth rudiments of embryonic mice. I. Transfilter interaction of embryonic incisor tissues. J. exp. Zool
.
165
,
155
170
.
Kollar
,
E. J.
(
1966
).
An in vitro study of hair and vibrissae development in embryonic mouse skin
.
J. invest. Derm
.
46
,
254
262
.
Kollar
,
E. J.
(
1970
).
The induction of hair follicles by dermal papillae
.
J. invest. Derm
. (In the Press.)
Kollar
,
E. J.
&
Baird
,
G. R.
(
1968
).
Effect of beta-2-thienylalanine on developing mouse tooth germs in vitro
.
J. dent. Res
.
47
,
433
443
.
Kollar
,
E. J.
&
Baird
,
G. R.
(
1969
).
The influence of the dental papilla on the development of tooth shape in embryonic mouse tooth germs
.
J. Embryol. exp. Morph
.
21
,
131
148
.
Kollar
,
E. J.
&
Baird
,
G. R.
(
1970a
).
Tissue interaction in embryonic mouse tooth germs. I. Reorganization of the dental epithelium during tooth germ reconstruction
.
J. Embryol. exp. Morph
.
24
,
159
171
.
Kollar
,
E. J.
&
Baird
,
G. R.
(
1970b
).
Tissue interactions in developing mouse tooth germs
.
In Studies in Dental Morphology
(ed.
A.
Dahlberg
),
The University of Chicago Press
. (In the Press.)
Lillie
,
F. R.
&
Wang
,
H.
(
1941
).
Physiology of development of the feather. V. Experimental morphogenesis
.
Physiol. Zool
.
14
,
103
133
.
Lillie
,
F. R.
&
Wang
,
H.
(
1944
).
Physiology and development of the feather. VII. An experimental study of induction
.
Physiol. Zool
.
17
,
1
31
.
McLoughlin
,
C. B.
(
1968
).
Interaction of epidermis with various types of foreign mesenchyme
.
In Epithelial-Mesenchymal Interactions
(ed.
R.
Fleischmajer
&
R. E.
Billingham
), pp.
244
251
. Baltimore: The Williams and Wilkins Co.
Rawles
,
M. E.
(
1963
).
Tissue interactions in scale and feather development as studied in dermal-epidermal recombinations
.
J. Embryol. exp. Morph
.
11
,
765
789
.
Schmidt
,
R. W.
(
1956
).
Simultaneous fixation and decalcification of tissue
.
Lab. Invest
.
5
,
306
307
.
Sengel
,
P.
(
1964
).
The determinism of the skin and cutaneous appendages of the chick embryo
.
In The Epidermis
(ed.
W.
Montagna
&
W. C.
Lobitz
, Jr
.), pp.
15
34
.
New York and London
:
Academic Press
.
Slavkin
,
H. C.
&
Bavetta
,
L. A.
(
1968
).
Odontogenic epithelial-mesenchymal interactions in vitro
.
J. dent. Res
.
47
,
779
785
.
Wang
,
H.
(
1943
).
Morphogenetic functions of the epidermal and dermal components of the papilla in feather regeneration
.
Physiol. Zool
.
16
,
325
.
Wessells
,
N. K.
(
1967
).
Differentiation of epidermis and epidermal derivatives
.
New Engl. J. Med
.
277
,
21
33
.