The objective of this article is to evaluate the role of retinoids in the developing head and face. This article covers two lines of evidence that strongly support a role for retinoids in craniofacial development. First, the specific effects of exogenous retinoids on the head and face are covered and mechanisms for the specificity discussed. Second, the function of endogenous retinoids in facial development is discussed in relation to the distribution of retinoid-binding substances in the face. Finally, the interaction of retinoids with other genes known to be expressed in the face as well as other factors required for facial growth is discussed.
References
1.
Abbott, B.D., M.W. Harris, and L.S. Birnbaum: Etiology of Retinoic Acid-Induced Cleft Palate Varies with the Embryonic Stage. Teratology40:533-558 (1989).
2.
Alles, A.J. and K. Sulik: Retinoic-Acid-Induced Limb-Reduction Defects: Perturbation of Zones of Programmed Cell Death as a Pathogenetic Mechanism. Teratology40:163-171 (1989).
3.
Altaba, R. and T. Jessel: Retinoic Acid Modified Mesodermal Patterning in Early Xenopus Embryos. Genes Dev. 5:175-187 (1991).
4.
Benbrook, D., E. Lernhardt, and M. Pfahl: A New Retinoic Acid Receptor Identified from a Hepatocellular Carcinoma. Nature333:669-672 (1988).
5.
Benke, P.J.: The Isotretinoin Teratogen Syndrome. JAMA251(24):3267-3269 (1984).
6.
Brand, N., M. Petkovich, A. Krust, P. Chambon, H. De Thé, A. Marchio, P. Tiollais, and A. Dejean: Identification of a Second Human Retinoic Acid Receptor. Nature332:850-853 (1988).
7.
Cho, E.W.Y. and E.M. De Robertis: Differential Activation of Xenopus Homeobox Genes by Mesoderm Inducing Growth Factors and Retinoic Acid. Genes Dev. 4:1910-1916 (1990).
8.
Chisaka, O. and M.R. Capecchi: Regionally Restricted Developmental Defects Resulting from Targeted Disruption of the Mouse Homeobox Gene hox-1.5. Nature350:473-479 (1991).
9.
Chytil, F. and D.E. Ong: In: The Retinoids, Vol. 2, pp. 90-123, (M. B. Sporn, A. B. Roberts, D. S. Goodman, Eds.) Academic Press, Orlando, Florida (1984).
10.
Couly, G.F. and N.M. Le Douarin: Head Morphogenesis in Embryonic Avian Chimeras: Evidence for a Segmental Pattern in the Ectoderm Corresponding to the Neuro-meres. Development108:543-558 (1990).
11.
Couly, G.F. and N.M. Le Douarin: Mapping of the Early Neural Primordium in Quail-Chick Chimeras. II. The Prosencephalic Neural Plate and Neural Folds: Implications for the Genesis of Cephalic Human Congenital Abnormalities. Dev. Biol. 120:198-214 (1987).
12.
Creech-Kraft, J., B. Lofberg, I. Chahoud, G. Bochert, and H. Nau: Teratogenicity and Placental Transfer of All-trans-, 13-cis-, 4-Oxo-all-trans-, and 4-Oxo-13-cis-Retinoic Acid after Administration of a Low Oral Dose during Organogenesis in Mice. Toxicol. Appl. Pharmacol. 100:162-176 (1989).
13.
Davidson, D.R., A. Crawley, R.E. Hill, and C. Tickle: Position-Dependent Expression of Two Related Homeobox Genes in Developing Vertebrate Limbs. Nature352:429-431 (1991).
14.
Dencker, L., E. Annerwall, C. Busch, and U. Eriksson: Localisation of Specific Retinoid-Binding Sites and Expression of Cellular Retinoic Acid-Binding Protein (CRABP) in the Early Mouse Embryo. Development110:343-352 (1990).
15.
Dencker, L., R. D'Argy, B. Danielsson, H. Ghanous, and G.O. Sperber: Saturable Accumulation of Retinoic Acid in Neural and Neural Crest-Derived Cells in Early Embryonic Development. Dev. Pharmacol. Ther. 10:212-223 (1987).
16.
De Thé, H., A. Marchio, P. Tiollais, and A. Dejean: Differential Expression and Ligand Regulation of the Retinoic Acid Receptor a and β Genes. EMBO J. 8(2):429-433 (1989).
17.
Devlin, C.J., P.M. Brickell, E.R. Taylor, A. Hornbruch, R.K. Craig, and L. Wolpert: In Situ Hybridization Reveals Differential Spatial Distribution of mRNAs for Type I and Type II Collagen in the Chick Limb Bud. Development103:111-118 (1988).
18.
Diewert, V.M.: Correlation between Mandibular Retrognathia and Induction of Cleft Palate with 6-Aminonicotinamide in the Rat. Teratology19:213-228 (1979).
19.
Diewert, V.M. and R.M. Pratt: Selective Inhibition of Mandibular Growth and Induction of Cleft Palate by Diazo-oxo-norleucine (DON) in the Rat, Teratology20:37-52 (1979).
20.
Diewert, V.M. and Wang: Recent Advances in Primary Palate and Midface Morphogenesis Research. Critical Rev. Oral Biol. Med. (this issue). (1992).
21.
Dollé, P., E. Ruberte, P. Kastner, M. Petkovich, C.M. Stoner, L. Gudas, and P. Chambon: Differential Expression of the Genes Encoding the Retinoic Acid Receptors a, β, γ, and CRABP in the Developing Limbs of the Mouse. Nature342:702-705 (1989).
22.
Dollé, P., E. Ruberte, P. Leroy, G. Morriss-Kay, and P. Chambon: Retinoic Acid Receptors and Cellular Retinoid Binding Proteins. I. A Systematic Study of Their Differential Pattern of Transcription during Mouse Organogenesis. Development110:1133-1151 (1990 ).
23.
Durston, A., J.P.M. Timmermans, W.J. Hage, H.F.J. Hendriks, N.J. De Vries, M. Heideveld, and P.D. Niewkoop: Retinoic Acid Causes an Anteroposterior Transformation in the Developing Central Nervous System. Nature340:140-144 (1989).
24.
Evans, R.M.: The Steroid and Thyroid Hormone Receptor Super-family. Science240:889-895 (1988).
25.
Gavin, B.J., A.J. McMahon, and A.P. McMahon: Expression of Multiple Novel Wnt-1/int-1-Related Genes during Fetal and Adult Mouse Development. Genes Dev. 4:2319-2332 (1990).
26.
Giguere, V., E. Ong, P. Segui, and R.M. Evans: Identification of a Receptor for the Morphogen Retinoic Acid. Nature330:624-629 (1987).
27.
Giguere, V., M. Shago, R. Zirngibl, P. Tate, J. Rossant, and S. Varmuza: Identification of a Novel Isoform of the Retinoic Acid Receptor γ Expressed in the Mouse Embryo. Mol. Cell. Biol. 10:2335-2340 (1990).
28.
Goulding, E.H. and R.M. Pratt: Isotretinoin Teratogenicity in Mouse Whole Embryo Culture. J. Craniofac. Genet. Dev. Biol. 6:99-112 (1986).
29.
Goulding, M.D., G. Chalepakis, U. Deutsch, J.R. Erselius, and P. Gruss: Pax-3, a Novel Murine DNA Binding Protein Expressed during Early Neurogenesis. EMBO J. 10(5):1135-1147 (1991).
30.
Green, S. and P. Chambon: Nuclear Receptors Enhance Our Understanding of Transcriptional Regulation. Trends Genet. 4:309-314 (1988).
31.
Hall, B.K.: Morphogenesis of the Skeleton: Epithelial or Mesenchymal Control? In: Trends in Vertebrate Morphology. ( H. Splechtna, H. Hilgers, Eds.) Gustav Fisher Verlag, New York ( 1989).
32.
Hall, B.K.: Initiation of Osteogenesis by Mandibular Mesenchyme of the Embryonic Chick in Response to Mandibular and Non-Mandibular Epithelia. Arch. Oral Biol. 23:1157-1161 (1978).
33.
Hall, B.K. and S. Horstadius: The Neural Crest. Oxford University Press, London (1988).
34.
Hall, B.K.: Tissue Interactions and the Initiation of Osteogenesis and Chondrogenesis in the Neural Crest-Derived Mandibular Skeleton of the Embryonic Mouse as Seen in Isolated Murine Tissues and in Recombinations of Murine and Avian Tissues. J. Embryol. Exp. Morphol. 58:251-264 (1980).
35.
Hamburger, V. and H.L. Hamilton: A Series of Normal Stages in the Development of the Chick Embryo. J. Morphol. 88:49-92 (1951).
36.
Hassel, J.R., J.H. Greenberg, and M.C. Johnston: Inhibition of Cranial Neural Crest Cell Development by Vitamin A in the Cultured Chick Embryo. J. Embryol. Exp. Morphol. 39:267-271 (1977).
37.
Heine, U.I., A.B. Roberts, E.F. Munoz, N.S. Roche, and M.B. Sporn: Effects of Retinoid Deficiency on the Development of the Heart and Vascular System of the Quail Embryo. Virchows Arch. Cell. Pathol.50:135-152 (1985).
38.
Heuer, J.G., C.S. Von Bartheld, Y. Kinoshita, P.C. Everes, and M. Bothwell: Alternating Phases of FGF Receptor and NGF Receptor Expression in the Developing Chicken Nervous System. Neuron5:283-296 (1990).
39.
Hill, R.M.: Isotretinoin Teratogenicity. Lancet1465 (1984).
40.
Hill, R.E., P.F. Jones, A.R. Rees, C.M. Sime, J.J. Justice, N.G. Copeland, N.A. Jenkins, E. Graham, and D.R. Davidson: A New Family of Mouse Homeo Box-Containing Genes: Molecular Structure, Chromosomal Location, and Developmental Expression of Hox-7.1. Genes Dev. 3:26-37 (1989).
41.
Hoffmann, B., J.M. Lehmann, X-K. Zhang, T. Hermann, M. Husmann, G. Graupner, and M. Pfahl: A Retinoic Acid Receptor-Specific Element Controls the Retinoic Acid Receptor-β Promoter. Mol. Endocrinol. 4(11):1727-1736 (1990).
42.
Holland, P.W.H.: Homeobox Genes and the Vertebrate Head. Development (Suppl) 17-24 (1988).
43.
Horton, W.E., Y. Yamada, and J.R. Hassell: Retinoic Acid Rapidly Reduces Cartilage Matrix Synthesis by Altering Gene Transcription in Chondrocytes. Dev. Biol. 123:508-516 (1987).
44.
Hunt, P., D. Wilkinson, and R. Krumlauf: Patterning the Vertebrate Head: Murine Hox 2 Genes Mark Distinct Subpopulations of Premigratory and Migrating Cranial Neural Crest. Development112:43-50 (1991).
45.
Hunt, P. and R. Krumlauf: Deciphering the Hox Code: Clues to Patterning Branchial Regions of the Head. Cell66:1075-1978 (1991 ).
46.
Ispizua-Belmonte, J-C., C. Tickle, P. Dollé, L. Wolpert, and D. Duboule: Expression of the Homeobox Hox-4 Genes and the Specification of Position in Chick Wing Development. Nature350:585-589 (1991).
47.
Jelinek, R. and A. Kistler: Effect of Retinoic Acid upon the Chick Embryonic Morphogenetic Systems. I. The Embryotoxicity Dose Range. Teratology23:191-195 (1981).
48.
Jetten, A.M., M.A. Anderson, H. Deas, R. Kagechika, J. Lotan, I. Rearick, and K. Shudo: New Benzoic Acid Derivatives with Retinoid Activity: Lack of Direct Correlation between Biological Activity and Binding to Cellular Retinoic Acid Binding Protein. Cancer Res.47:3523-3527 (1987 ).
49.
Johnston, M.C.: A Radioautographic Study of the Migration and Fate of Cranial Neural Crest Cells in the Chick Embryo. Anat. Rec. 156:143-156 (1966).
50.
Jones, C.M., K.M. Lyons, and B.L.M. Hogan: Involvement of Bone Morphogenetic Protein-4 (BMP-4) and Vgr-1 in Morphogenesis and Neurogenesis in the Mouse. Development111:531-542 (1991).
51.
Joyner, A.L., K. Herrup, A. Auerbach, C.A. Davis, and J. Rossant: Subtle Cerebellar Phenotype in Mice Homozygous for a Targeted Deletion of the En-2 Homeobox. Science251:1239-1243 (1991).
52.
Kalter, H. and J. Warkany: Experimental Production of Congenital Malformations in Mammals by Metabolic Procedure. Physiol. Rev. 39:69-115 (1959).
53.
Kessel, M. and P. Gruss: Homeotic Transformations of Murine Vertebrae and Concomitant Alteration of Hox Codes Induced by Retinoic Acid. Cell67:89-104 (1991).
54.
Knudson, P.A.: Congenital Malformations of Lower Incisors and Molars in Exencephalic Mouse Embryos, Induced by Hypervitaminosis A. Acta Odontol. Scand. 24:55-91 (1966).
55.
Krust, A., P. Kastner, M. Petkovich, A. Zelent, and P. Chambon: A Third Human Retinoic Acid Receptor, hRARγ. Proc. Natl. Acad. Sci. U.S.A. 86:5310-5314 (1989 ).
Langille, R.M., D.F. Paulsen, and M. Solursh: Differential Effects of Physiological Concentrations of Retinoic Acid In Vitro on Chondrogenesis and Myogenesis in Chick Craniofacial Mesenchyme. Differentiation40:84-92 (1989).
58.
Larosa, G.J. and L.J. Gudas: Early Retinoic Acid-Induced F9 Teratocarcinoma Stem Cell Gene ERA-1: Alternate Splicing Creates Transcripts for a Homeobox-Containing Protein and One Lacking the Homeobox. Mol. Cell. Biol. 8(9):3906-3917 (1988).
59.
Le Lièvre, C.S.: Participation of Neural Crest-Derived Cells in the Genesis of the Skull in Birds. J. Embyol. Exp. Morphol. 47:17-37 (1978).
60.
Le Douarin, N.: The Neural Crest. Cambridge University Press, Cambridge (1982).
61.
Leroy, P., A. Krust, A. Zelent, C. Mendelsohn, J.-M. Gamier, P. Kastner, A. Dierich, and P. Chambon: Multiple Isoforms of the Mouse Retinoic Acid Receptor a Are Generated by Alternative Splicing and Differential Induction by Retinoic Acid. EMBO J.10:59-69 (1991).
62.
Lufkin, T., A. Dierich, J. Lemeur, M. Mark, and P. Chambon: Disruption of the Hox-1.6 Homeobox Gene Results in Defects in a Region Corresponding to Its Rostral Domain of Expression. Cell66:1105-1119 (1991).
63.
Lumsden, A., N. Sprawson, and A. Graham: Segmental Origin and Migration of Neural Crest Cells in the Hind-brain Region of the Chick Embryo. Development113:1281-1292 (1991).
64.
Lüscher, B., P.J. Mitchell, T. Williams, and R. Tjian: Regulation of Transcription Factor AP-2 by the Morphogen Retinoic Acid and by Second Messengers. Genes Dev. 3:1507-1517 (1989).
65.
Lyons, K.M., R.W. Pelton, and B. Hogan: Organogenesis and Pattern Formation in the Mouse: RNA Distribution Patterns Suggest a Role for Bone Morphogenetic Protein-2A (BMP-2A). Development109:833-844 (1990).
66.
Mackenzie, A., G.L. Leeming, A.K. Jowett, M.W.J. Ferguson, and P.T. Sharpe: The Homeobox Gene Hox 7.1 has Specific Regional and Temporal Expression Patterns During Early Murine Craniofacial Embryogenesis, Especially Tooth Development In Vivo and In Vitro, Development. 111:269-285 (1991).
67.
Maden, M., P. Hunt, U. Eriksson, A. Kuroiwa, R. Krumlauf, and D. Summerbell: Retinoic Acid-Binding Protein, Rhombomeres and the Neural Crest. Development111:35-44 (1991).
68.
Maden, M., D.E. Ong, and F. Chytil: Retinoid-Binding Protein Distribution in the Developing Mammalian Nervous System. Development109:75-80 (1990).
69.
Maden, M., D.E. Ong, D. Summerbell, and F. Chytil: Spatial Distribution of Cellular Protein Binding to Retinoic Acid in the Chick Limb Bud. Nature335:733-735 (1988).
70.
Manglesdorf, D.J., E.S. Ong, J.A. Dyck, and R.M. Evans: Nuclear Receptor that Identifies a Novel Retinoic Acid Response Pathway. Nature345:224-229 (1990).
71.
Mendelsohn, C., E. Ruberte, M. Lemeur, G. Morriss-Kay, and P. Chambon: Developmental Analysis of the Retinoic Acid-Inducible RAR-β2 Promoter in Transgenic Animals. Development113(3):723-734 (1991).
72.
Mitchell, P.J., P.M. Timmons, J.M. Herbert, P.W.J. Rigby, and R. Tjian: Transcription Factor AP-2 is Expressed in Neural Crest Cell Lineages during Mouse Embryogenesis. Genes Dev. 5:105-119 (1991).
73.
Mitrani, E., T. Ziv, G. Thomsen, Y. Shimoni, D.A. Melton, and A. Bril: Activin Can Induce the Formation of Axial Structures and Is Expressed in the Hypoblast of the Chick. Cell63:495-501 (1990).
74.
Morriss, G.M. and P.V. Thorogood: An Approach to Cranial Neural Crest Cell Migration and Differentiation in Mammalian Embryos. In: Development in Mammals, Vol. 3, pp. 363-441. (M. H. Johnson, Ed.) Elsevier / North Holland, Amsterdam (1978).
75.
Nichols, D.H.: Neural Crest Formation in the Head of the Mouse Embryo as Observed Using a New Histological Technique. J. Embryol. Exp. Morphol. 64:105-120 (1981).
76.
Nichols, D.H.: Formation and Distribution of Neural Crest Mesenchyme to the First Pharyngeal Arch Region of the Mouse Embryo. Am. J. Anat. 176:221-231 (1986).
77.
Noden, D.M.: An Analysis of the Migratory Behaviour of Avian Cephalic Neural Crest Cells. Dev. Biol. 42:106-130 (1975).
78.
Noden, D.M.: The Control of Avian Cephalic Neural Crest Cytodifferentiation. I. Skeletal and Connective Tissues. Dev. Biol. 67:296-312 (1978).
79.
Noden, D.M.: The Role of the Neural Crest in Patterning of Avian Cranial Skeletal, Connective and Muscle Tissues. Dev. Biol. 96:144-165 (1983).
80.
Noden, D.M.: Interactions between Cephalic Neural Crest Cells and Mesodermal Populations. In: Development and Evolutionary Aspects of the Neural Crest, pp. 89-119. (P. Maderson Ed.) Wiley, New York (1987).
81.
Noden, D.M.: Interactions and Fates of Avian Craniofacial Mesenchyme. Development (Suppl)103:121-140 (1988).
82.
Nohno, T., K. Muto, S. Noji, T. Saito, and S. Taniguchi: Isoforms of Retinoic Acid Receptor β Expressed in the Chicken Embryo. Biochem. Biophys. Acta1089:273-275 (1991).
83.
Noji, S., T. Nohno, E. Koyama, K. Muto, K. Ohyama, Y. Aoki, K. Tamura, K. Ohusugi, H. Ide, S. Taniguchi, and T. Saito: Retinoic Acid Induces Polarizing Activity but Is Unlikely To Be a Morphogen in the Chick Limb Bud. Nature350:83-86 (1991).
84.
Osumi-Yamashita, N., S. Noji, T. Nohno, E. Koyama, H. Doi, K. Eto, and S. Taniguchi: Expression of Retinoic Acid Receptor Genes in Neural Crest-Derived Cells during Mouse Facial Development. FEBS Letts. 264:71-74 (1990).
85.
Perez-Castro, A.V., L.E. Toth-Rogler, L-N. Wei, M.C. Nguyen-Huu: Cellular Retinoic Acid-Binding Protein and the Cellular Retinol-Binding Protein during Mouse Embryogenesis, Proc. Natl. Acad. Sci. U.S.A. 86:8813-8817 (1989).
86.
Petkovich, M., N.J. Brand, A. Krust, and P. Chambon: A Human Retinoic Acid Receptor Which belongs to the Family of Nuclear Receptors. Nature330:440-450 (1987).
87.
Richman, J.M. and Z. Crosby: Differential Growth of Facial Primordia in Chick Embryos: Responses of Facial Mesenchyme to Basic Fibroblast Growth Factor (bFGF) and Serum in Micromass Culture. Development109:341-348 (1990).
88.
Richman, J.M. and C. Tickle: Epithelia are Interchangeable between the Facial Primordia of Chick Embryos and Morphogenesis is Controlled by the Mesenchyme. Dev. Biol. 136:201-210 (1989).
89.
Richman, J. and C. Tickle: Epithelial-Mesenchymal Interactions in the Outgrowth of Limb Buds and Facial Primordia in Chick Embryos Dev. Biol. in press.
90.
Robert, B., D. Sassoon, B. Jacq, W. Gehring, and M. Buckingham: Hox-7, a Mouse Homeobox Gene with a Novel Pattern of Expression during Embryogenesis. EMBO J., 8:91-100 (1989).
91.
Rosa, F.: Teratogenicity of Isotretinoin. Lancet513 (1983).
92.
Rossant, J., R. Zirngibl, D. Cado, M. Shago, and V. Giguere: Expression of a Retinoic Acid Response Element-hsplacZ Transgene Defines Specific Domains of Transcriptional Activity during Mouse Embryogenesis. Genes Dev. 5:1333-1344 (1991 ).
93.
Rowe, A., J.M. Richman, and P.M. Brickell: Retinoic Acid Treatment Alters the Distribution of Retinoic Acid Receptor-β Transcripts in the Embryonic Chick Face. Development111:1007-1016 (1991a).
94.
Rowe, A., N.C.S. Eager, and P.M. Brickell: A Member of the RXR Nuclear Receptor Family Is Expressed in the Neural Crest-Derived Cells of the Developing Chick Periphral Nervous System. Development111:771-778 (1991b).
95.
Rowe, A., J.M. Richman, and P.M. Brickell: Development of the Spatial Pattern of Retinoic Acid Receptor-β Transcripts in Embryonic Chick Facial Primordia. Development114:805-813 (1992).
96.
Ruberte, E., P. Dollé, A. Krust, A. Zelent, G. Morriss-Kay, and P. Chambon: specific Spatial and Temporal Distribution of Retinoic Acid Receptor Gamma Transcripts during Mouse Embryogenesis. Development108:213-222 (1990).
97.
Ruberte, E., P. Dollé, P. Chambon, and G. Morriss-Kay: Retinoic Acid Receptors and Cellular Retinoid Binding Proteins. II. Their Differential Pattern of Transcription during Early Morphogenesis in Mouse Embryos. Development111:45-60 (1991).
98.
Satre, M.A. and D.M. Kochhar: Elevations in the Endogenous Levels of the Putative Morphogen Retinoic Acid in Embryonic Mouse Limb-Buds Associated with Limb Dysmorphogenesis. Dev. Biol. 133:529-536 (1989).
99.
Saunders, J.W. and M.T. Gassling: Ectodermal-Mesodermal Interactions in the Origin of Limb Symmetry. In: Epithelial-Mesenchymal Interactions, pp. 78-97. ( R. Fleishcmayer, R. E. Billingham, Eds.) Williams and Wilkins, Baltimore (1968).
100.
Silver, P.H.S.: In Ovo Experiments Concerning the Eye, the Orbit, and Certain Juxta-Orbital Structures, in the Chick Embryo. J. Embryol. Exp. Morphol. 10:423-450 (1962).
101.
Simeone, A., D. Acampora, L. Arcionic, P.W. Andrews, E. Boncinelli, and F. Mavilio: Sequential Activation of Hox2 Homeobox Genes by Retinoic Acid in Human Embryonal Carcinoma Cells. Nature346:766 (1990).
102.
Sive, H.L., B.W. Draper, R.M. Harland, and H. Weintraub: Identification of a Retinoic Acid-Sensitive Period During Primary Axis Formation in Xenopus Laevis. Genes Dev. 4:932-942 (1990).
103.
Smith, S.M. and G. Eichele: Temporal and Regional Differences in the Expression of Distinct Retinoic Acid Receptor-β Transcripts in the Chick Embryo. Development111:245-252 (1991).
104.
Smith, J.C., B.M.J. Price, K. Van Nimmen, and D. Huylebroeck: Identification of a Potent Xenopus, Mesoderm-Inducing Factor as a Homologue of Activin A. Nature345:729-731 (1990).
105.
Summerbell, D.: The Effect of Local Application of Retinoic Acid to the Anterior Margin of the Developing Chick Limb. J. Embryol. Exp. Morphol. 78:269-289 (1983).
106.
Tabin, C.J.: Retinoids, Homeoboxes, and Growth Factors: Toward Molecular Models for Limb Development. Cell66:199-217 (1991).
107.
Tamarin, A., A. Crawley, J. Lee, and C. Tickle: Analysis of Upper Beak Defects in Chicken Embryos Following Treatment with Retinoic Acid. J. Embryol. Exp. Morphol. 84:105-123 (1984).
108.
Tamura, K., H. Kagechika, Y. Hashimoto, K. Shudo, K. Ohsugi, and H. Ide: Synthetic Retinoids, Retinobenzoic Acids, Am80,Am580, and Ch55 Regulate Morphogenesis in Chick Limb Bud. Cell Differ. Dev. 32:17-26 (1990).
109.
Tan, S.S. and G. Morriss-Kay: Analysis of Cranial Neural Crest Cell Migration and Early Fates in Postimplantation Rat Chmieras. J. Embryol. Exp. Morphol. 88:231-247 (1986).
110.
Thaller, C. and G. Eichele: Identification and Spatial Distribution of Retinoids in the Developing Chick Limb Bud. Nature327:625-628 (1987).
111.
Thaller, C. and G. Eichele: Characterization of Retinoid Metabolism in the Developing Chick Limb Bud. Development103:473-483 (1988).
112.
Thaller, C. and G. Eichele: Isolation of 3,4-Didehydroretinoic Acid, A Novel Morphogenetic Signal in the Chick Wing Bud. Nature345:815-819 (1990).
113.
Thorogood, P., J. Bee, and K. Von Der Mark: Transient Expression of Collagen Type II at Epitheliomesenchymal Interfaces during Morphogenesis of the Cartilaginous Neurocranium. Dev. Biol. 116:497-509 (1986).
114.
Thorogood, P.: The Developmental Specification of the Vertebrate Skull. Development (Suppl.)103:141-153 (1988).
115.
Tickle, C., B.M. Alberts, L. Wolpert, and J. Lee: Local Application of Retinoic Acid to the Limb Bud Mimics the Action of the Polarizing Region. Nature296:564-566 (1982).
116.
Tickle, C., A. Crawley, and J. Farrar: Retinoid Acid Application to Chick Wing Buds Leads to a Dose-Dependent Reorganization of the Apical Ectodermal Ridge that is Mediated by the Mesenchyme. Development106:691-705 (1989).
117.
Tickle, C.: The Polarizing Region and Limb Development. In: Development in Mammals, Vol. 4, pp. 101-134. (M. H. Johnson, Ed.) (1980).
118.
Tickle, C.: The Number of Polarizing Region Cells Required to Specify Additional Digits in the Developing Chick Wing. Nature289:295-298 (1981).
119.
Tickle, C.: Retinoic Acid and Chick Limb Development. Development (Suppl.)1:113-121 (1991).
120.
Tyler, M.S.: Epithelial Influences on Membrane Bone Formation in the Maxilla of the Embryonic Chick. Anat. Rec. 192:225-234 (1978).
121.
Tyler, M.S. and B.K. Hall: Epithelial Influences on Skeletogenesis in the Mandible of the Embryonic Chick. Anat. Rec. 188:229-240 (1977).
122.
Tyler, M.S. and D.P. McCobb: The Genesis of Membrane Bone in the Embryonic Chick Maxilla: Epithelial-Mesenchymal Tissue Recombination Studies. J. Embryol. Exp. Morphol. 56:269-281 (1980).
123.
Vaessen, M.-J., J.H.C. Meijers, D. Bootsma, andG. Van Kessel: The Cellular Retinoic-Acid-Binding Protein is Expressed in Tissues Associated With Retinoic-Induced Malformations. Development110:371-378 (1990).
124.
Wanaka, A., J. Milbrandt and E.M. Johnson: Expression of FGF Receptor Gene in Rat Development. Development111:455-468 (1991).
125.
Wanek, D.M., D.M. Gardiner, K. Muneoka, and S.V. Bryant: Conversion by Retinoic Acid of Anterior Cells into ZPA Cells in the Chick Wing Bud. Nature350:81-83 (1991).
126.
Webster, W.S., M.C. Johnston, E.J. Lammer, and K.K. Sulik: Isotretinoin Embryopathy and the Cranial Neural Crest: An In Vivo and In Vitro Study. J. Craniofac. Genet. Dev. Biol. 6:211-222 (1986).
127.
Wedden, S.E., M.R. Lewin-Smith, and C. Tickle: The Patterns of Chondrogenesis of Cells from Facial Primordia of Chick Embryos in Micromass Cultures. Dev. Biol. 117:71-82 (1986).
128.
Wedden, S.E. and C. Tickle: Quantitative Analysis of the Effect of Retinoids on Facial Morphogenesis. J. Craniofac. Genet. Dev. Biol. (Suppl.)2:169-178 (1986).
129.
Wedden, S.E.: Pattern Formation and the Effects of Retinoids on Chick Facial Morphogenesis. Thesis, University of London (1986).
130.
Wedden, S.E.: Effects of Retinoids on Chick Face Development J. Craniofac. Gen. Dev. Biol. 11:326-337 (1991).
131.
Wedden, S.E., M.R. Lewin-Smith, and C. Tickle: Analysis of the Effects of Retinoids on Cartilage Differentiation in Micromass Cultures of Chick Facial Primordia and the Relationship to a Specific Facial Defect. Dev. Biol. 122:78-89 (1987).
132.
Werler, M.M., E.J. Lammer, L. Rosenberg, and A.A. Mitchell: Maternal Vitamin A Supplementation in Relation to Selected Birth Defects. Teratology42:497-503 (1990).
133.
Wolpert, L.: Positional Information Revisited. Development (Suppl.)107:3-12 (1989).
134.
Wood, A., D.E. Ashhurst, A. Corbett, and P. Thorogood: The Transient Expression of Type II Collagen at Tissue Interfaces during Mammalian Craniofacial Development. Development111:955-968 (1991).
135.
Zelent, A., A. Krust, M. Petkovich, P. Kastner, and P. Chambon: Cloning of Murine a and β Retinoic Acid Receptors and a Novel Receptor Gamma Predominantly Expressed in Skin. Nature339:714-717 (1989).
136.
Zelent, A., C. Mendelsohn, P. Kastner, A. Krust, J.-M. Gamier, F. Ruffenach, P. Leroy and P. Chambon: Differentially Expressed Isoforms of the Mouse Retinoic Acid Receptor β are Generated by Usage of Two Promotors and Alternative Splicing. EMBO J. 10:71-81 (1991).
