Study of Pax6 mutant rat revealed the association between upper incisor formation and midface formation

In this study, we investigated the process of supernumerary upper incisor formation in the Pax6 mutant rat, rSey2/rSey2, which exhibits a facial cleft between the medial nasal and maxillary processes. Histological investigation and epithelial labeling studies of wild type rat embryos indicated that the upper incisor develops by fusion of two primary dental placodes (PDPs) in the medial nasal process with a contribution from the epithelium of the maxillary process. In the rSey2/rSey2 embryo, both PDPs are formed but they stay apart, then subsequently these PDPs independently develop into upper incisor tooth buds. In order to examine if the failure of the two placodes to fuse is due to the cleft between the maxillary and medial nasal processes, maxillary and medial nasal process fusion was inhibited with a barrier in wild type embryos. This resulted in the maintenance of the two distinct PDPs. These results demonstrate that fusion of the facial processes reduces the number of odontogenic placodes and is required to assemble all components at one site for rat upper incisor formation. The results also provide further insight into the mechanism of supernumerary incisor formation in human cleft lip conditions. Developmental Dynamics 235:2134–2143, 2006. © 2006 Wiley‐Liss, Inc.

[1]  H. Lesot,et al.  Origin of the Deciduous Upper Lateral Incisor and its Clinical Aspects , 2006, Journal of dental research.

[2]  S. Iseki,et al.  Dual odontogenic origins develop at the early stage of rat maxillary incisor development , 2006, Anatomy and Embryology.

[3]  D. Goldowitz,et al.  Disruption of cerebellar granule cell development in the Pax6 mutant, Sey mouse. , 2005, Brain research. Developmental brain research.

[4]  R. Kist,et al.  Reduction of Pax9 gene dosage in an allelic series of mouse mutants causes hypodontia and oligodontia. , 2005, Human molecular genetics.

[5]  Z. Kozmík.  Pax genes in eye development and evolution. , 2005, Current opinion in genetics & development.

[6]  R. Lang.  Pathways regulating lens induction in the mouse. , 2004, The International journal of developmental biology.

[7]  J. Treisman.  How to make an eye , 2004, Development.

[8]  S. Modino,et al.  Stem-cell-based Tissue Engineering of Murine Teeth , 2004, Journal of dental research.

[9]  J. Piatigorsky,et al.  Requirement for Pax6 in corneal morphogenesis: a role in adhesion , 2003, Journal of Cell Science.

[10]  R. Hill,et al.  The roles of Pax6 in the cornea, retina, and olfactory epithelium of the developing mouse embryo. , 2003, Developmental biology.

[11]  B. Costa,et al.  Dental anomalies of the permanent lateral incisors and prevalence of hypodontia outside the cleft area in complete unilateral cleft lip and palate. , 2003, The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association.

[12]  B. Costa,et al.  Dental Anomalies of the Permanent Lateral Incisors and Prevalence of Hypodontia outside the Cleft Area in Complete Unilateral Cleft Lip and Palate , 2003 .

[13]  K. Harii,et al.  Ectopically localized HNK‐1 epitope perturbs migration of the midbrain neural crest cells in Pax6 mutant rat , 2001, Development, growth & differentiation.

[14]  A. McMahon,et al.  Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. , 2000, Development.

[15]  J. Kere,et al.  Cusp patterning defect in Tabby mouse teeth and its partial rescue by FGF. , 1999, Developmental biology.

[16]  C. Hui,et al.  The Shh signalling pathway in tooth development: defects in Gli2 and Gli3 mutants. , 1998, Development.

[17]  L. See,et al.  Distribution patterns of primary and permanent dentition in children with unilateral complete cleft lip and palate. , 1998, The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association.

[18]  M. Kaufman,et al.  Genetic background effects on dental and other craniofacial abnormalities in homozygous small eye (Pax6Sey/Pax6Sey) mice , 1997, Anatomy and Embryology.

[19]  M. Nakafuku,et al.  Pax-6 is involved in the specification of hindbrain motor neuron subtype. , 1997, Development.

[20]  R. Balling,et al.  Antagonistic Interactions between FGF and BMP Signaling Pathways: A Mechanism for Positioning the Sites of Tooth Formation , 1997, Cell.

[21]  S. Iseki,et al.  Cranial anomaly of homozygous rSey rat is associated with a defect in the migration pathway of midbrain crest cells , 1997, Development, growth & differentiation.

[22]  K. Eto,et al.  Contribution of early-emigrating midbrain crest cells to the dental mesenchyme of mandibular molar teeth in rat embryos. , 1996, Developmental biology.

[23]  M. Kaufman,et al.  Craniofacial abnormalities in homozygous Small eye (Sey/Sey) embryos and newborn mice. , 1995, Journal of anatomy.

[24]  D. Davidson,et al.  The role of Pax-6 in eye and nasal development. , 1995, Development.

[25]  K. Eto,et al.  Uchida rat (rSey): a new mutant rat with craniofacial abnormalities resembling those of the mouse Sey mutant. , 1994, Differentiation; research in biological diversity.

[26]  J. Vonesch,et al.  Multiple developmental origin of the upper incisor in mouse: histological and computer assisted 3-D-reconstruction studies. , 1993, The International journal of developmental biology.

[27]  G. Saunders,et al.  Mouse Small eye results from mutations in a paired-like homeobox-containing gene , 1991, Nature.

[28]  B. Hogan,et al.  Small eye (Sey): a mouse model for the genetic analysis of craniofacial abnormalities. , 1988, Development.

[29]  T. Ooe,et al.  On the early development of human dental lamina. , 1957, Okajimas folia anatomica Japonica.

[30]  S. Iseki,et al.  Tissue origins and interactions in the mammalian skull vault. , 2002, Developmental biology.

[31]  I. Thesleff,et al.  The role of growth factors in tooth development. , 2002, International review of cytology.

[32]  R. Maas,et al.  The genetic control of early tooth development. , 1997, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[33]  D. Wilkinson.  Wholemount in situ hybridization of vertebrate embryos , 1992 .

[34]  M. Strassburg,et al.  [Morphogenesis of the dental lamina. II. Histological studies on the earliest phases of differentiation in the mouse dental lamina]. , 1971, Deutsche zahnarztliche Zeitschrift.