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Previous Article | Next Article 
Molecular and Cellular Biology, February 2003, p. 1075-1084, Vol. 23, No. 3
0270-7306/03/$08.00+0 DOI: 10.1128/MCB.23.3.1075-1084.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Lerner Research Institute, Department of Cancer Biology, Cleveland Clinic Foundation,1 Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio,6 Department of Anatomy, University of Wisconsin Medical School, Madison, Wisconsin,3 Center for Craniofacial Molecular Biology, University of Southern California School of Dentistry, Los Angeles, California,4 Department of Oral Biology, School of Dental Medicine,5 Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York2
Received 24 June 2002/ Returned for modification 6 August 2002/ Accepted 7 November 2002
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ABSTRACT |
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INTRODUCTION |
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The nuclear factor I (NFI) family of transcription-replication factors is encoded by four genes in mammals (NFI-A, -B, -C, and -X) and a single gene in Drosophila melanogaster and Caenorhabditis elegans (8, 14, 23). Prokaryotic homologues of the NFI genes have not been identified. NFI was discovered as a protein required for adenovirus DNA replication in vitro (19, 20), but it is now clear that NFI proteins play an important role in the expression of many cellular genes (reviewed in reference 8). NFI-C/CTF was the initial NFI gene cloned (24) and contains a prototypical proline-rich transcriptional activation domain, as well as a heptamer repeat homologous to the C-terminal domain of RNA polymerase II (18). Because products of the four NFI genes are often coexpressed (3) and bind to similar DNA sequences (15), it has been difficult to determine the roles of individual NFI family members in gene expression during development. We are analyzing the role of NFI genes in mouse development by generating mice deficient in each of the four NFI genes.
We disrupted the Nfic gene in mice by removal of its second exon, which encodes the NFI-C/CTF DNA-binding and dimerization domain. The most striking defect in Nfic-/- mice is that their molar teeth form no roots. In addition, their mature mandibular incisors are thin and brittle, and their maxillary incisors are dysmorphic. Consistent with these tooth defects, Nfic-/- mice exhibit compromised feeding on standard lab chow, resulting in increased morbidity and mortality. Since loss of Nfic is the first mouse mutation to specifically affect root development, these mice should be an important tool for understanding the molecular pathways essential for this process.
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MATERIALS AND METHODS |
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1.3 kb of Nfic from an NdeI site 98 bp 5' of exon 2 to an NheI site 700 bp 3' of exon 2. The negatively selectable gene cassette MCI-TK (herpes simplex virus thymidine kinase with a mutant polyomavirus enhancer [17]) was adjacent to the shorter region of Nfic homology in the opposite transcriptional orientation. A total of 5 x 106 E14-1 mouse embryonic stem (ES) cells (12) were electroporated with 5 µg of XhoI-linearized targeting vector and then selected in 0.2 mg/ml of G418 (Gibco-BRL) and 2 µM ganciclovir (Roche Laboratories) for 6 days. Colonies were isolated and expanded twice in 96-well plates. Two plates were cryopreserved, and two were used for DNA isolation and Southern blot analyses. PCR genotyping. Toe or 0.5-cm tail-tip biopsies were shaken at 55°C overnight in 0.5 ml of tail lysis buffer (0.05 M Tris-Cl, pH 8.0; 0.1 M EDTA; 0.5% sodium dodecyl sulfate), including 0.5 mg of proteinase K/ml. Then, 1 µl of the lysate diluted 1:25 in H2O was analyzed in 20-µl multiplex PCRs (2.5 U of platinum Taq DNA polymerase (Gibco-BRL), 1.5 mM MgCl2, 0.2 mM concentrations of each deoxynucleoside triphosphate, 1x Rediload (Research Genetics), 1x PCR buffer (supplied with the Taq), and five primers at 0.2 µM each). The following two Nfic-specific primers (a and c), Neo-specific primer (b), and two mouse Y chromosome-specific primers (SRY) were used: a (5'-CATCTGTGTGAAACAGTCTGG-3'), b (5'-CCGCTTCCTCGTGCTTTACGG-3'), c (5'-AGCAGCTCATCCTTCACCGCG-3'), SRY1 (5'-AACAACTGGGCTTTGCACATTG-3'), and SRY2 (5'-GTTTATCAGGGTTTCTCTCTAGC-3'). PCR products were resolved on 2.5% agarose gels and visualized with ethidium bromide.
RT-PCR. Total RNA was isolated by using TRIzol reagent (Gibco-BRL) according to the manufacturer's instructions. RNA from mandible was purified over a G50 spin column (Roche) prior to reverse transcription (RT). cDNA was generated from 2 to 5 µg of RNA by using Superscript (Gibco-BRL) according to the manufacturer's random-prime protocol. A total of 1 µl of each RT product was analyzed by PCR with a sense primer from exon 1 (5'-GATCGGCCTCACGGGCCGATGTATTCCTCCCCGCTCTGC-3') and an antisense primer from exon 3 (5'-TTGCTGTCCTCCTGGTCTGAGC-3'). Products were resolved on 2.5% agarose gels. Analysis of Nfia, Nfib, Nfix, amelogenin, ameloblastin, dentin sialophosphoprotein (DSPP), and ß2-microglobulin transcript levels was done by real-time quantitative PCR with an ABI 7700 or Bio-Rad real-time thermocycler with SYBRgreen detection. The primer sequences and conditions are available upon request.
Mouse rearing. The initial 17 F1 litters were fed a diet of autoclaved mouse chow (Purina 5010 and, for breeders, Purina 5021) and autoclaved distilled water. For studies requiring adults, several grams of the soft transgenic dough diet (S3472; Bio-Serv) were added to cages twice per week beginning 3 days prior to the P21 wean.
Histology and in situ hybridization. Postnatal mice were anesthetized with isoflurane and cardiac perfused with 4% paraformaldehyde-phosphate-buffered saline (PBS). Heads were removed and depelted, the craniums were evacuated, and the skulls were decalcified by soaking them in formaldehyde-formic acid at 4°C overnight. After paraffin embedding, 4-µm sections were cut and stained with hematoxylin and eosin (H&E). For embryos, fixing, embedding, sectioning, and in situ hybridization with 35S-labeled Nfic cRNA sense and antisense probes were performed as described previously (3, 16). The control sense probe shows a low background level of silver grains (not shown). For postnatal tissue in situ hybridizations, digoxigenin (DIG)-labeled Nfic sense and antisense cRNA probes were prepared by using the T7/Sp6 DIG RNA labeling kit (Roche). Sections were deparaffinized and hybridized according to the manufacturer's protocol. Briefly, sections were hydrated, treated for 20 min with proteinase K (20 µg/ml), washed with PBS, fixed in 4% paraformaldehyde, washed again in PBS, incubated with 0.2 N HCl for 10 min to inhibit endogenous alkaline phosphatase, and acetylated by incubation for 10 min in 0.1 M triethanolamine containing 0.25% acetic anhydride. After a washing step, hybridization was performed overnight at 50°C in hybridization solution (50% deionized formide, 10% dextran sulfate, 1x Denhardt solution, 4x SSC [1x SSC is 0.15 M NaCl plus 0.015 M sodium citrate], 10 mM dithiothreitol, 1 mg of yeast tRNA/ml, 1 mg of salmon sperm DNA/ml) containing the DIG-UTP-labeled Nfic cRNA sense or antisense probes. After being washed for 30 min with 2x SSC-50% formamide and 10 min each in 2x SSC and 0.2x SSC at 50°C, sections were incubated for 30 min with blocking solution, followed by incubation for 1 h with blocking solution containing 1:500 sheep anti-DIG-alkaline phosphatase Fab fragments. After being washed, DIG probes were detected by incubating the sections with alkaline phosphatase substrates (368 µg of nitroblue tetrazolium salt and 184 µg of BCIP (5-bromo-4-chloro-3-indolylphosphate) in 1 ml of 100 mM Tris-HCl, 100 mM NaCl, and 50 mM MgCl2) until the color was developed. Sections were then used directly or counterstained for 2 to 3 min with methyl green, air dried, and mounted by using VectaMount (Vector Laboratories).
Skull bones and molar teeth isolation. Mouse heads were depelted, the muscles and fascia were clipped away, and the brains and eyes were removed before soaking the heads in 1% KOH for 3 days. After three rinses with H2O, the heads were individually incubated in 50 mM Tris-Cl (pH 8.0), 0.5% SDS, and 0.2 mg of proteinase K/ml at 55°C for 20 min and then washed with H2O. Molars of Nfic-/- mice separated from the jaw during proteolysis, whereas those of the other Nfic genotypes were isolated by crown extraction or fracturing the mandible or maxilla.
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RESULTS |
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150 bp of the Y chromosome. Southern blot analysis of these same DNAs confirmed the PCR results (data not shown). To show that the targeted Nfic allele was null, we analyzed Nfic transcripts from brain and liver RNA of adult littermates of each Nfic genotype. Total RNA was isolated, reverse transcribed, and the cDNA was used as a template in PCRs with Nfic exon 1-specific (forward) and exon 3-specific (reverse) primers (Fig. 1D). As predicted, the PCR produced a single 638-bp product from brain and liver cDNA of the wild-type (+/+) mouse. This product is from a transcript that includes exon 2 (532 bp) and the termini of exons 1 and 3 (Fig. 1D, lanes +/+). The PCR generated two products from brain and liver cDNA of the Nfic+/- littermate (Fig. 1D, lanes +/-). The larger product corresponds to the wild-type transcript, whereas the smaller product corresponds to a 106-bp product resulting from a direct splice of exon 1 to 3. Only the smaller product was amplified from brain and liver cDNA of the Nfic-/- littermate (Fig. 1D, lanes -/-). Sequencing of the smaller product confirmed that it is generated from a direct splice from exon 1 to exon 3 (data not shown). Because the exon 1-exon 3 splice junction is out of frame, these aberrantly spliced Nfic transcripts are predicted to encode a 31-amino-acid missense polypeptide that terminates in exon 3.
Viability, growth, and fertility of Nfic-/- mice. Our initial 17 heterozygote crosses produced 154 F1 progeny distributed in a Mendelian ratio: 33 wild-type (21.4%), 87 Nfic+/- (56.5%), and 34 Nfic-/- mice (22.1%). We noted in early litters that postweaning Nfic-/- mice became severely runted compared to their wild-type or Nfic+/- littermates (Fig. 2A). Continued rearing of Nfic-/- mice on standard lab chow resulted in continued runting and premature death (Fig. 2B and data not shown). Upon discovery of tooth defects in the Nfic-/- mice (see below, Fig. 3 to 6), we added a soft-dough dietary supplement 3 days prior to weaning and continued the diet supplementation of Nfic-/- mice postweaning. The dough diet supplementation allowed all (n = 18) Nfic-/- mice to survive longer than 3 months and into adulthood. Of three male and four female healthy adult Nfic-/- mice bred with Nfic+/- partners, all but one female mated successfully. The resulting litters were of normal size, the Nfic genotype ratio was the expected 1:1 (Nfic+/-:Nfic-/-), and the litters were reared successfully. These data indicate that Nfic-/- mice have greatly increased morbidity and mortality when fed standard lab chow and that a soft diet supplement rescues the mortality, permitting survival and fertility.
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A similar analysis of coronal sections of maxillae revealed a less pronounced but clearly abnormal maxillary incisor development in Nfic-/- mice (Fig. 4). The maxillary incisors of wild-type (not shown) and Nfic+/- animals were substantially thicker than those of Nfic-/- mice (Fig. 4A versus B). The maxillary incisors of wild-type and heterozygous animals have dentin around the entire circumference and enamel on one surface (Fig. 4C [expanded in panel E]). In contrast, the maxillary incisors of Nfic-/- animals have near-normal labial dentin and enamel deposition but nearly absent lingual dentin deposition, leading to a grossly nonsymmetric structure (Fig. 4D [expanded in panel F]).
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10% smaller than those of their wild-type and heterozygous littermates (Fig. 6D versus C). No such size difference was noted in maxillae (Fig. 6A). To examine earlier stages of alveolar bone formation, we isolated skeletonized mandibles from P15 littermates. In contrast to what was seen with adult skulls, molars fell out of both +/+ and -/- mouse mandibles (Fig. 6E and F). At this age alveolar bone has begun to surround the emerging molar roots in +/+ mice, whereas no such bone formation is seen in the tooth sockets of -/- mice (Fig. 6F, +/+ versus -/-). In contrast, bone formation between the teeth appears similar in both +/+ and -/- animals (Fig. 6F, +/+ versus -/-).
Nfic expression during tooth development. To assess when and where Nfic is expressed during tooth development, we performed in situ hybridization with the Nfic-specific probe we described previously (3). During tooth bud development at E15.5, Nfic is expressed strongly in the mesenchymal cells of the dental papilla and weakly in the epithelial components (Fig. 7A and B ). When root formation is beginning at P8 (Fig. 7C), Nfic is expressed strongly in most epithelial tissues of the tooth, including ameloblasts; in odontoblasts; in surrounding mesenchymal tissues, including the stellate reticulum; and in the dental papilla of the molars and incisor. No staining is seen with the control sense probe (Fig. 7D, F, and H). At P14, when molar root formation is in progress, Nfic expression appears more restricted being present within the odontoblasts and preodontoblasts of the molars (Fig. 7E and G) and within the periodontal ligament and developing bone (Fig. 7G). Figure 7G and H are magnifications of the boxed regions of Fig. 7E and F, respectively. Thus, Nfic is expressed at multiple stages of tooth development and strongly in odontoblasts and preodontoblasts during root formation.
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1 type I collagen in the Nfic-/- mice (Fig. 8, lane Col). These data are consistent with the histology of P15 Nfic-/- animals that show abnormal mandibular incisor and molar root development.
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DISCUSSION |
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The specific combination of defects seen in Nfic-/- mice (loss of molar roots with apparently normal crown formation and severe mandibular incisor disruption with milder maxillary incisor defects) is unique to this mouse and indicates a relatively late role for Nfic in tooth development. In contrast, loss of either Msx-1 (1) or Lef1 (33) causes the arrest of tooth development at the bud stage, which precludes analysis of late events in tooth formation. Loss of both Dlx-1 and Dlx-2 results in complete agenesis of maxillary molars, whereas mandibular molars and incisors appear normal (22, 30). This differential effect of loss of the Dlx genes emphasizes the apparently unique molecular requirements of mandibular versus maxillary molar development. In addition, the lack of a dental phenotype in individual Dlx knockouts demonstrates the apparent redundancy of some transcription factors in maxillary molar development. Redundant functions in tooth formation have also been observed for the Gli family of transcription factors. The loss of Gli3 had no observable dental phenotype, whereas the loss of Gli2 resulted in relatively mild abnormalities in maxillary incisor development (10). However, in Gli2/Gli3 double mutants there was no normal tooth development with apparent arrest at the early bud (incisors) or prebud stages (molars). Given this redundancy in Dlx and Gli family members, it will be of interest to determine whether the Nfic-/- phenotype is affected by loss of other NFI genes.
Compared to the study of early tooth development described above, few molecules are known to be required for late events in tooth morphogenesis, including root formation. For example, although Msx-1 is essential for early tooth bud formation, transplantation and rescue studies have shown that Msx-1 is not essential for later cap and crown formation but appears to again play a role in the long-term survival of odontoblasts and dental pulp (1). Thus, it is difficult to predict which, if any, of the genes identified as essential for early tooth development function in molar root formation. Two mutations, Tabby (Ta) and Downless (Dl), are known to affect late tooth development (32). However, these mutations affect both molar crown and root formation, whereas the Nfic-/- mutation affects predominantly root formation. Since Nfic is expressed during both molar crown and root formation (Fig. 7), while the major phenotype we see is restricted to root formation (Fig. 3 to 6), it will be of interest to determine whether one of the other NFI genes compensates for the loss of Nfic during crown formation.
Molar root development begins at P9 by outgrowth of a collar of cells (Hertwig's epithelial root sheath) from the molar crown. These epithelial cells then induce the differentiation of dental papillary mesenchymal cells into odontoblasts which, through migration, dentin deposition, and mineralization form the hard structure of the root. Our data suggest that this collar of cells either fails to grow out of the crown and/or fails to induce odontoblast differentiation (Fig. 5). Whether this molar root defect is related mechanistically to the abnormal incisor development seen in the Nfic-/- mice is unclear. However, it is intriguing that the maxillary incisor defects seen in Nfic-/- mice appear to be due to a failure of differentiation and/or dentin formation in lingual regions of the incisor (Fig. 4F, arrow), much as root formation requires appropriate differentiation and dentin formation at the base of the molar (Fig. 5). Unfortunately, there are no genes or signaling pathways known to be expressed solely in the epithelial root sheath, and the incisors' cellular homologue of the molar root sheath has not been well characterized. In addition, since incisors continue to grow throughout adult life, whereas molar root and crown development and growth terminate, it is possible that there are incisor-specific mechanisms that allow for continuous growth. It will be important to define gene expression patterns in the affected regions of both the molars and incisors in the Nfic-/- mice to determine whether these defects are due to changes in similar regulatory pathways. The Nfic-/- mouse should provide a unique and important resource to determine the transcriptional and cell-signaling pathways essential for molar root formation.
Given the previously noted widespread expression of Nfic during development (3), it is perhaps surprising that the phenotype of the Nfic-/- mouse is so restricted. Indeed, most other mouse mutations affecting tooth development also affect other developmental programs, including hair follicle and skin formation (Ta and Dl), bone formation (Msx1 and -2), craniofacial development (Msx1 and -2, Pax9), cardiac development (Msx1), and others. However, some of these genes are expressed in migrating neural crest cells that populate many organ systems, which most likely explains their pleiotropic phenotypes (2, 6). Detailed genetic analysis of Nfic interactions with other genes will be important in determining whether Nfic functions in other organ systems. Also, since a number of human dental and craniofacial defects appear to be due to mutations in human homologues of murine tooth development genes (11, 28, 34), it will be important to determine whether mutations in NFIC underlie any of the uncharacterized odontogenic syndromes.
The defects seen here are in striking contrast to the neuroanatomical defects present in Nfia-/- animals (agenesis of the corpus callosum, hydrocephalus, etc. [4]) and the lung defects seen in Nfib-/- animals (9) and indicate that these three NFI family members each have unique and essential roles in mouse development. The apparent lack of compensatory changes in the other NFI family members in both Nfic (Fig. 8) and Nfia-/- mice suggest that there is little if any "feedback" between the family members. This is surprising because there is frequently overlapping expression of the different family members during development (3). However, although the three phenotypes are very different, it is possible that similar changes in transcriptional pathways underlie the anatomical defects seen in all three mutants. We are currently taking two approaches to finding out whether Nfic and Nfia interact in similar transcriptional and developmental pathways in mice: (i) we are generating Nfia/Nfic double-knockout mice to assess their phenotype and (ii) we are assessing the earliest changes in gene expression patterns in the affected tissues of Nfic-/- and Nfia-/- mice to determine the pathways disrupted in each animal. These approaches should help us to understand the pathways underlying the anatomical defects seen in these animals and allow us to determine whether these two NFI genes share common regulatory mechanisms in mice.
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ACKNOWLEDGMENTS |
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This work was supported in part by Public Health Service grants HD34901 from the National Institute of Child Health and Development and DK58401 from the National Institute of Diabetes and Digestive and Kidney Diseases to R.M.G.
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FOOTNOTES |
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REFERENCES |
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2. Chai, Y., X. Jiang, Y. Ito, P. Bringas, Jr., J. Han, D. H. Rowitch, P. Soriano, A. P. McMahon, and H. M. Sucov. 2000. Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development 127:1671-1679.[Abstract]
3. Chaudhry, A. Z., C. E. Lyons, and R. M. Gronostajski. 1997. Expression patterns of the four nuclear factor I genes during mouse embryogenesis indicate a potential role in development. Dev. Dyn. 208:313-325.[CrossRef][Medline]
4. das Neves, L., C. Duchala, F. Godinho, M. Haxhiu, C. Colmenares, W. Macklin, C. Campbell, K. Butz, and R. Gronostajski. 1999. Disruption of the murine nuclear factor I-A gene (Nfia) results in perinatal lethality, hydrocephalus and agenesis of the corpus callosum. Proc. Natl. Acad. Sci. USA 96:11946-11951.
5. Dassule, H. R., P. Lewis, M. Bei, R. Maas, and A. P. McMahon. 2000. Sonic hedgehog regulates growth and morphogenesis of the tooth. Development 127:4775-4785.[Abstract]
6. Ferguson, C. A., A. S. Tucker, and P. T. Sharpe. 2000. Temporospatial cell interactions regulating mandibular and maxillary arch patterning. Development 127:403-412.[Abstract]
7. Fletcher, C. F., N. A. Jenkins, N. G. Copeland, A. Z. Chaudhry, and R. M. Gronostajski. 1999. Exon structure of the nuclear factor I DNA-binding domain from Caenorhabditis elegans to mammals. Mamm. Genome 10:390-396.[CrossRef][Medline]
8. Gronostajski, R. M. 2000. Role of NFI/CTF gene family in transcription and development. Gene 249:31-45.[CrossRef][Medline]
9. Grunder, A., T. T. Ebel, M. Mallo, G. Schwarzkopf, T. Shimizu, A. E. Sippel, and H. Schrewe. 2002. Nuclear factor I-B (Nfib)-deficient mice have severe lung hypoplasia. Mech. Dev. 112:69-77.[CrossRef][Medline]
10. Hardcastle, Z., R. Mo, C. C. Hui, and P. T. Sharpe. 1998. The Shh signaling pathway in tooth development: defects in Gli2 and Gli3 mutants. Development 125:2803-2811.[Abstract]
11. Headon, D. J., S. A. Emmal, B. M. Ferguson, A. S. Tucker, M. J. Justice, P. T. Sharpe, J. Zonana, and P. A. Overbeek. 2001. Gene defect in ectodermal dysplasia implicates a death domain adapter in development. Nature 414:913-916.[CrossRef][Medline]
12. Hooper, M., K. Hardy, A. Handyside, S. Hunter, and M. Monk. 1987. HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature 326:292-295.[CrossRef][Medline]
13. Kettunen, P., J. Laurikkala, P. Itaranta, S. Vainio, N. Itoh, and I. Thesleff. 2000. Associations of FGF-3 and FGF-10 with signaling networks regulating tooth morphogenesis. Dev. Dyn. 219:322-332.[CrossRef][Medline]
14. Kruse, U., F. Qian, and A. E. Sippel. 1991. Identification of a fourth nuclear factor I gene in chicken by cDNA cloning: NFIX. Nucleic Acids Res. 19:6641.
15. Kruse, U., and A. E. Sippel. 1994. Transcription factor nuclear factor I proteins form stable homo- and heterodimers. FEBS Lett. 348:46-50.[CrossRef][Medline]
16. Lyons, G., M. Ontell, R. Cox, D. Sassoon, and M. Buckingham. 1990. The expression of myosin genes in developing skeletal muscle in the mouse embryo. J. Cell Biol. 111:1465-1476.
17. Mansour, S. L., K. R. Thomas, and M. R. Capecchi. 1988. Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature 336:348-357.[CrossRef][Medline]
18. Meisterernst, M., L. Rogge, C. Donath, I. Gander, F. Lottspeich, R. Mertz, T. Dobner, and R. Fockler. 1988. Isolation and characterization of the porcine nuclear factor I (NFI) gene. FEBS Lett. 236:27-32.[CrossRef][Medline]
19. Nagata, K., R. Guggenheimer, T. Enomoto, J. Lichy, and J. Hurwitz. 1982. Adenovirus DNA replication in vitro identification of a host factor that stimulates synthesis of the preterminal protein-dCMP complex. Proc. Natl. Acad. Sci. USA 79:6438-6442.
20. Nagata, K., R. A. Guggenheimer, and J. Hurwitz. 1983. Specific binding of a cellular DNA replication protein to the origin of replication of adenovirus DNA. Proc. Natl. Acad. Sci. USA 80:6177-6181.
21. Peters, H., A. Neubuser, K. Kratochwil, and R. Balling. 1998. Pax9-deficient mice lack pharyngeal pouch derivatives and teeth and exhibit craniofacial and limb abnormalities. Genes Dev. 12:2735-2747.
22. Qiu, M., A. Bulfone, I. Ghattas, J. J. Meneses, L. Christensen, P. T. Sharpe, R. Presley, R. A. Pedersen, and J. L. Rubenstein. 1997. Role of the Dlx homeobox genes in proximodistal patterning of the branchial arches: mutations of Dlx-1, Dlx-2, and Dlx-1 and -2 alter morphogenesis of proximal skeletal and soft tissue structures derived from the first and second arches. Dev. Biol. 185:165-184.[CrossRef][Medline]
23. Rupp, R., U. Kruse, G. Multhaup, U. Gobel, K. Beyreuther, and A. Sippel. 1990. Chicken NFI/TGGCA proteins are encoded by at least three independent genes: NFI-A, NFI-B and NFI-C with homologues in mammalian genomes. Nucleic Acids Res. 18:2607-2616.
24. Santoro, C., N. Mermod, P. Andrews, and R. Tjian. 1988. A family of human CCAAT-box-binding proteins active in transcription and DNA replication: cloning and expression of multiple cDNAs. Nature 334:218-224.[CrossRef][Medline]
25. Sarkar, L., M. Cobourne, S. Naylor, M. Smalley, T. Dale, and P. T. Sharpe. 2000. Wnt/Shh interactions regulate ectodermal boundary formation during mammalian tooth development. Proc. Natl. Acad. Sci. USA 97:4520-4524.
26. Soriano, P., C. Montgomery, R. Geske, and A. Bradley. 1991. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell 64:693-702.[CrossRef][Medline]
27. St Amand, T. R., Y. Zhang, E. V. Semina, X. Zhao, Y. Hu, L. Nguyen, J. C. Murray, and Y. Chen. 2000. Antagonistic signals between BMP4 and FGF8 define the expression of Pitx1 and Pitx2 in mouse tooth-forming anlage. Dev. Biol. 217:323-332.[CrossRef][Medline]
28. Stockton, D. W., P. Das, M. Goldenberg, R. N. D'Souza, and P. I. Patel. 2000. Mutation of PAX9 is associated with oligodontia. Nat. Genet. 24:18-19.[CrossRef][Medline]
29. Thesleff, I., and P. Sharpe. 1997. Signalling networks regulating dental development. Mech. Dev. 67:111-123.[CrossRef][Medline]
30. Thomas, B. L., A. S. Tucker, M. Qui, C. A. Ferguson, Z. Hardcastle, J. L. Rubenstein, and P. T. Sharpe. 1997. Role of Dlx-1 and Dlx-2 genes in patterning of the murine dentition. Development 124:4811-4818.[Abstract]
31. Tucker, A. S., A. Al Khamis, and P. T. Sharpe. 1998. Interactions between Bmp-4 and Msx-1 act to restrict gene expression to odontogenic mesenchyme. Dev. Dyn. 212:533-539.[CrossRef][Medline]
32. Tucker, A. S., D. J. Headon, P. Schneider, B. M. Ferguson, P. Overbeek, J. Tschopp, and P. T. Sharpe. 2000. Edar/Eda interactions regulate enamel knot formation in tooth morphogenesis. Development 127:4691-4700.
33. van Genderen, C., R. M. Okamura, I. Farinas, R. G. Quo, T. G. Parslow, L. Bruhn, and R. Grosschedl. 1994. Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. Genes Dev. 8:2691-2703.
34. Wilkie, A. O., Z. Tang, N. Elanko, S. Walsh, S. R. Twigg, J. A. Hurst, S. A. Wall, K. H. Chrzanowska, and R. E. Maxson, Jr. 2000. Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification. Nat. Genet. 24:387-390.[CrossRef][Medline]
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