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Origin of the Deciduous Upper Lateral Incisor and its Clinical Aspects
1 Department of Teratology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic; Correspondence: * corresponding author, marhor{at}biomed.cas.cz
The upper lateral incisor in humans is often affected by dental anomalies that might be explained developmentally. To address this question, we investigated the origin of the deciduous upper lateral incisor (i2) in normal human embryos at prenatal weeks 6–8. We used serial frontal histological sections and computer-aided 3D reconstructions. At embryonic days 40-42, two thickenings of the dental epithelia in an "end-to-end" orientation were separated by a groove at the former fusion site of the medial nasal and maxillary processes. Later, these dental epithelia fused, forming a continuous dental lamina. At the fusion site, i2 started to develop. The fusion line was detectable on the i2 germ until the 8th prenatal week. The composite origin of the i2 may be associated with its developmental vulnerability. From a clinical aspect, a supernumerary i2 might be a form of cleft caused by a non-fusion of the dental epithelia.
Key Words: lateral incisor • dental epithelium • human tooth development • orofacial cleft • dental anomalies
In humans, the upper lateral incisor is often affected by dental anomalies such as agenesis, alterations of shape and size, and supernumeraries (Ravn, 1971; Jarvinen and Lehtinen, 1981; Stamatiou and Symons, 1991). In a normal population of 3- to 3.5-year-old children, Ravn (1971) found that half of the supernumerary teeth in the primary dentition were maxillary lateral incisors. Upper lateral incisor abnormalities are frequently associated with different types of orofacial clefts (Jordan et al., 1966; Tsai et al., 1998). In children with a unilateral complete cleft lip and palate, Tsai et al.(1998) observed four distribution patterns of the primary upper lateral incisor on the cleft side: (a) one lateral incisor located distally to the alveolar cleft, (b) one lateral incisor located mesially to the alveolar cleft, (c) the absence of the lateral incisor, and (d) the presence of two lateral incisors—one tooth on each side of the alveolar cleft. In a normal population, the prevalence of supernumerary teeth is less than 1% for the primary dentition (e.g., Ravn, 1971; Jarvinen and Lehtinen, 1981). However, in patients with a cleft lip, the incidence of a supernumerary lateral incisor varies between 40% and 73% in the primary dentition (Böhn, 1963; Hansen and Mehdinia, 2002). In the permanent dentition, supernumerary lateral incisors were found in 42% of cleft patients (Böhn, 1963). Supernumerary lateral incisors are more frequent in the deciduous dentition than in the permanent one (Böhn, 1963; Tsai et al., 1998; Hansen and Mehdinia, 2002).
The morphology of the human face is established between the 5th and 10th prenatal weeks. An upper jaw arch is formed by the fusion of the paired medial nasal and maxillary facial processes (Figs. 1A, 1B, 1D
The developmental origin of the upper deciduous lateral incisor is not clear. It is generally believed that the human upper deciduous incisors originate from the medial nasal process. In macaques, it has been suggested that the primary maxillary central and lateral incisors are derived from the medial nasal and maxillary processes, respectively (Wei et al., 2000). In humans, Ooë (1957) has proposed that the upper lateral incisor can originate partly on the maxillary and partly on the medial nasal process. The aim of our study was to search for the origin of the deciduous upper lateral incisor in normal human embryos at prenatal weeks 6–8, to elucidate the reasons for the developmental vulnerability of this tooth.
The development of the upper dental epithelium was examined in a collection of serial histological sections held by the Department of Teratology IEM in Prague. The collection consists of 53 normal embryos (artificial interruption of unwanted gravidity) and was constituted from the 1960s to the 1980s.
Histology
3D Reconstructions
Contours of the dental and adjacent oral epithelium were drawn from the serial histological sections at 10-µm intervals (magnification x120–260, depending on the size of the specimen), under a LEICA DMLB (Leica Microsystems, Wetzlar, Germany) or JENAVAL (Carl Zeiss, Jena, Germany) microscope equipped with a drawing chamber.The superimposition of the serial drawings was performed by the "best-fit" method. The digitalization and the correlation of successive images have previously been described (Lesot et al., 1996). Three-dimensional images were generated by a volume-rendering program (Sun Voxel, Sun Microsystems, Santa Clara, CA, USA).
During prenatal weeks 6–8, the place of fusion between the former medial nasal and maxillary outgrowths could be detected on the dental and vestibular epithelia in 3D reconstructions viewed from the mesenchymal aspect (Fig. 2  ; Appendix Figs. 4, 5, 6).
ED 40–42 The medial nasal and maxillary processes were already fused. Two thickenings of the dental epithelium were apparent, originating independently from the medial nasal and maxillary processes. These two dental thickenings, in an end-to-end orientation, were separated by a narrow groove. A line of fusion between the former facial processes was clearly detectable on 3D reconstructions. It was formed by a furrow going from the primary choana in the antero-lateral direction through the groove in the thickened dental epithelium, and further anteriorly to the epithelium of the oral vestibule (Figs. 2A, 2B  ; Appendix Figs. 4A, 4B).
ED 42–44
ED 44–46
Prenatal Week 8
Beginning of the 3rd Month
The human upper jaw arch is formed by the fusion of the paired medial nasal and maxillary processes. The frontonasal process (a developmental base of the medial nasal process) is formed by neural crest cells (NCC) derived from the mid- and forebrain regions in the mouse (Osumi-Yamashita et al., 1994). However, the first branchial arch (giving rise to the maxillary and mandibular processes) is populated by NCC from more caudal regions of the midbrain and the hindbrain in the rat (Imai et al., 1996). As the present results showed, the area of fusion of facial processes is where the upper lateral incisor germ develops. Accordingly, this germ could be populated by NCC of two different origins. However, verification of the NCC contribution would require an in vitro experiment with cell markers, which cannot be performed in human embryos.
The present study focused on the origin of the epithelial component of the upper lateral incisor germ. We used a natural marker—the furrow at the previous fusion site between medial nasal and maxillary processes. This furrow could be traced up to prenatal week 8 (Fig. 2
In humans, a thickened odontogenic epithelium can be identified in the 5th embryonic week on all the medial nasal and maxillary processes before their fusion (Ooë, 1957). The fusion of all components of the facial processes does not occur simultaneously. In macaques, the obliteration of the groove between the facial processes lags behind in the alveolus, compared with that in the lip (Wei et al., 2000). Generally, it is believed that the fusion of the human frontonasal, maxillary, and mandibular processes is complete by ED 38 (Tonge, 1967). The 3D reconstructions performed here clearly documented the fusion site between the medial nasal and maxillary processes. Although the facial processes proper have been fused, the thickenings of the dental epithelium were still separate at ED 40–42 (Figs. 2A, 2B
At the fusion site of the facial processes, the germ of the upper lateral incisor emerged, comprised of epithelium from both the medial nasal and maxillary processes (Fig. 2
The complex origin of the human upper lateral deciduous incisor can explain its developmental vulnerability, resulting in anomalies of number, shape, and size, frequently associated with orofacial clefts (Böhn, 1963; Hansen and Mehdinia, 2002). The presumed double origin of the upper lateral incisor (Ooë, 1957) has been used to explain the high incidence of two lateral incisors adjacent to the cleft, mesially and distally, in patients with a complete cleft lip and palate (CLP) (Tsai et al., 1998) (Figs. 1F
However, a supernumerary lateral incisor is also common in patients with an isolated cleft lip, who have an intact jaw without an alveolar cleft (Figs. 3B, 3C ), or even in people having no orofacial cleft (Ravn, 1971; Jarvinen and Lehtinen, 1981). These cases can be explained by the incomplete fusion of the facial processes: The medial nasal and maxillary processes fuse except for their dental epithelia, which remain separate (Fig. 1E). From this aspect, the duplicated upper lateral incisor in an intact jaw might hypothetically be considered as a form of cleft arising during the latest phase of fusion of facial processes. An incomplete fusion of the two dental components could also give rise to rare dental anomalies, such as fused or T-shaped incisors. From a clinical aspect, it is important that one consider the delay in fusion of the dental epithelia as part of the critical period of clefting. Moreover, the patients with supernumerary lateral incisors in an intact jaw can be at increased risk to carry some genetic predisposition for orofacial clefts. The presence of a supernumerary lateral incisor in otherwise clinically normal individuals could be used as a marker of possible cleft predisposition. As a similar marker, the ultrasonographic detection of orbicularis oris muscle defects has been proposed (Martin et al., 2000). Beside the supernumeraries, other dental anomalies can be observed in the lateral incisor region in cleft patients: one lateral incisor distal to the alveolar cleft, one lateral incisor mesial to the alveolar cleft, and the absence of a lateral incisor on the cleft side. The above-mentioned anomalies may be within the same spectrum and may be ranked according to the degree of hypoplasia (tissue insufficiency) of the facial processes. In humans, the fusion of facial processes proceeds from deeper to superficial. As fusion fails earlier, the more relevant (deeper) orofacial cleft occurs. Accordingly, the failing development of one or both components of the lateral incisor can be expected in more relevant cleft types that also affect hard tissues (cleft lip and alveolar process, CLP). One small lateral incisor located mesial or lateral to the alveolar cleft can reflect development of only one component of the lateral incisor (on the less hypoplastic facial process), while the second component (on the more hypoplastic process) did not form. The absence of the lateral incisor can be explained by the hypoplasia of both facial processes, including both components of the lateral incisor. From this aspect, the absence of the lateral incisor mesially and/or distally to the cleft could be the marker of the tissue insufficiency of the corresponding medial nasal and/or maxillary process. In contrast, the supernumerary lateral incisor might be more often associated with those cleft forms affecting only soft tissues (isolated soft-tissue cleft lip). The type of lateral incisor pattern could be used to subclassify patients with different forms of cleft into separate etiologic categories. The etiology of clefting according to the lateral incisor phenotype can be tested in families, specially in non-cleft siblings of cleft patients. The significantly higher frequency of dental anomalies has been found in the non-cleft siblings of cleft patients, compared with the control non-cleft group (Schroeder and Green, 1975). However, a precise ranking of patients into groups according to orofacial cleft type is necessary before the evaluation of the genetic background of this defect can proceed.
This work was supported by the Ministry of Education, Youth, and Sports of the Czech Republic (project COST B23.002), by the Grant Agency of the Czech Republic (GACR 304/05/2665), and by the Academy of Sciences of the Czech Republic (project AV0Z 50390512). We thank Professor J. Slipka for providing some of the human embryological material, MUDr. Ziva Mullerova, CSc, for photos of patients, and anonymous reviewers for their helpful comments.
A supplemental appendix to this article is published electronically only at http://www.dentalresearch.org. Received for publication September 23, 2004. Revision received September 1, 2005. Accepted for publication October 3, 2005.
Journal of Dental Research, Vol. 85, No. 2,
167-171 (2006)
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