The genetic pathways of development are only beginning to be revealed. But the tools now exist to allow the rapid isolation of genes that carry sequence motifs such as the homeobox, zinc finger or basic-helix loop helix that can mark genes of special developmental significance. Expression patterns are readily determined by in situ hybridization and in vivo developmental functions can be analyzed by generating mice with targeted mutations. Upstream regulators of genes can be identified by finding proteins that bind to cis-regulatory elements. Downstream targets are more difficult to find but there are polymerase chain reaction approaches to define sequences bound by transcription factors and subtractive library approaches to finding specific targets. Although an enormous amount of work remains to be done it is clear that the basic techniques necessary to understand the genetic program of mammalian development are now available. As these techniques are applied and refined we will elaborate the genetic regulatory pathways of organogenesis. This will be deeply satisfying from an intellectual perspective. It will also lead to a better understanding of birth defects and to better treatments of a variety of diseases that involve organ malformation or deterioration.
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Candia AF, Hu J, Crosby J, Lalley PA, Noden D, Nadeau JH, Wright CVE.Mox-1 andMox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. Development 116:1123–1136;1992.
Carroll SB, Scott MP. Localization of the fushi taraga protein duringDrosophila embryogenesis. Cell 43:47–57;1985.
Clarke MF, Kukowska-Latallo JF, Westin E, Smith M, Prochownik EU. Constitutive expression of a c-myb cDNA blocks Friend murine erythroleukemia cell differentiation. Mol Cell Biol 8:884–892;1988.
Craig RW, Bloch A. Early decline in c-myb oncogene expression in the differentiation of human myeloblastic leukemia (ML-1) cells induced with 12-0-tetradecanoylphorbol-13-acetate. Cancer Res 44:442–446;1984.
Dyson PJ, Poirier F, Watson RJ. Expression of c-myb in embryonal carcinoma cells and embryonal stem cells. Differentiation 42:24–27;1989.
Gonda TJ, Metcalf D. Expression ofmyb, myc, andfos proto-oncogenes during the differentiation of a murine myeloid leukaemia. Nature 310:249–251;1984.
Graham H, Papalopulu N, Krumlauf R. The murine andDrosophila homeobox gene complexes have common features of organization and expression. Cell 57:367–378;1989.
Hoeg TH, Levine M. Divergent homeobox proteins recognize similar DNA sequences in Drosophila. Nature 332:858–861;1988.
Joyner AL, Martin GR. En-1 and En-2, two mouse genes with sequence homology to theDrosophila engrailed gene: Expression during embryogenesis. Genes Dev 1:29–38;1987.
Kaur S, Singh G, Stock J, Schreiner C, Kier A, Yager K, Mucenski M, Scott W, Potter S. Dominant mutation of the murine Hox-2.2 gene results in developmental abnormalities. J Exp Zool 264:323–336;1992.
Kern MJ, Witte DP, Valerius MT, Aronow BJ, Potter SS. A novel murine homeobox gene isolated by a tissue specific PCR cloning strategy. Nucccleic Acids Res 20:5189–5195;1992.
Kessel M, Balling R, Gruss P. Variations of cervical vertebrae after expression of Hox-1.1 in transgenic mice. Cell 61:301–308;1990.
McGinnis W, Levine MS, Hafen E, Kuroiwa A, Gehring WJ. A conserved DNA sequence in homoeotic genes of theDrosophila melanogaster antennapedia and bithorax complexes. Nature 308:428–433;1984.
McGinnis W, Garber RL, Wirz J, Kuroiwa A, Gehring WJ. A homologous protein coding sequence inDrosophila homoeotic genes and its conservation in other metazoans. Cell 38:403–409;1984.
McLain K, Schreiner C, Yager K, Stock J, Potter S. Ectopic expression of Hox-2.3 induces craniofacial and skeletal malformations in transgenic mice. Mech Dev 39:3–16;1992.
McMahon J, Howe KM, Watson RJ. The induction of Friend erythroleukaemia differentiation is markedly affected by expression of a transfected c-myb cDNA. Oncogene 3:717–720;1988.
Mucenski M, McLain K, Kier AB, Swerdlow SH, Schreiner CM, Miller TA, Pietryga DW, Scott WJ, Potter SS. A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis. Cell 65:677–689;1991.
Schughart K, Kappen C, Ruddle F. Duplication of large genomic regions during the evolution of vertebrate homeobox genes. Proc Natl Acad Sci USA 86:7067–7071;1989.
Sheiness D, Gardinier M. Expression of a proto-oncogene (proto-myb) in hematopoietic tissues of mice. Mol Cell Biol 4:1206–1212;1984.
Singh G, Kaur S, Stock JL, Jenkins NA, Gilbert DJ, Copeland NG, Potter SS. Identification of 10 murine homeobox genes. Proc Natl Acad Sci USA 88:10706–10710;1991.
Thiele CJ, Cohen PS, Israel MA: Regulation of c-myb expression in human neuroblastoma cells during retinoic acid-induced differentiation. Mol Cell Biol 8:1677–1683;1988.
Torelli G, Venturelli D, Colo A, Zanni C, Selleri L, Moretti L, Calabretta B, Torelli U. Expression of c-myb protooncogene and other cell cycle-related genes in normal and neoplastic human colonic mucosa. Cancer Res 47:5266–5269;1987.
Treisman J, Gönczy P, Vashishtha M, Harris E, Desplan C. A single amino acid can determine the DNA binding specificity of homeodomain proteins. Cell 59:553–562;1989.
Weber BL, Westin EH, Clarke MF. Differentiation of mouse erythroleukemia cells enhanced by alternatively spliced c-myb mRNA. Science 249:1291–1293;1990.
Westin EH, Gallo RC, Arya SK, Eva A, Souza LM, Baluda MA, Aaronson SA, Wong-Staal F. Differential expression of theamv gene in human hematopoietic cells. Proc Natl Acad Sci USA 79:2194–2198;1982.
White R, Wilcox M. Regulation of the distribution of ultrabithorax proteins inDrosophila. Nature 318:563–567;1985.
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Potter, S.S. Selected aspects of homeobox gene function during mammalian development. J Biomed Sci 1, 204–208 (1994). https://doi.org/10.1007/BF02253303
- Gene circuitry
- Transcription factors
- Mutational analysis