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JOURNAL ARTICLES
Altered rhombomere-specific gene expression and hyoid bone differentiation in the mouse segmentation mutant, kreisler (kr)
M.A. Frohman, G.R. Martin, S.P. Cordes, L.P. Halamek, G.S. Barsh
Development 1993 117: 925-936;

Summary

Rhombomeres appear transiently in the vertebrate hindbrain shortly after neurulation and are thought to represent embryologic compartments in which the expression of different combinations of genes leads to segment-specific differentiation of the developing hindbrain, the cranial ganglia, and the branchial arches. To determine the extent to which gene expression is related to the formation of visible rhombomere boundaries, we have examined, by in situ hybridization, the expression of five rhombomere-specific genes in mouse embryos homozygous for the kreisler (kr) mutation, in which rhombomeres 4–7 are replaced by a smooth morphologically unsegmented neural tube. Using molecular probes specific for Hoxb-1 (Hox-2.9), Hoxb-3 (Hox-2.7), Hoxb-4 (Hox-2.6), Krox-20, or Fgf-3 (Int-2), we found that the kr mutation affects the expression of all the genes we examined, but, surprisingly, the altered patterns of expression are not restricted to that portion of the mutant hindbrain which is morphologically abnormal. Rostral expression boundaries of Hoxb-3 and Hoxb-4 are displaced from their normal positions at r4/5 and r6/7 to the approximate positions of r3/4 and r4/5, respectively. The expression domains of Krox-20 and Fgf-3 are also displaced in a rostral direction and the intensity of Fgf-3 hybridization is greatly reduced. The expression domain of Hoxb-1 is affected differently from the other genes in kr/kr embryos; its rostral boundary at r3/4 is intact but the caudal boundary is displaced from its normal location at r4/5 to the approximate position of r5/6. Because boundaries of gene expression for Hoxb-1 and Hoxb-4 are found in a region of the kr/kr hindbrain that lacks visible rhombomeres, establishment of regional identity, as reflected by differential gene expression, does not require overt segmentation. To investigate whether the altered patterns of gene expression we observed in the kr/kr embryonic hindbrain are associated with morphologic changes in the adult, we examined neural crest-derived tissues of the second and third branchial arches, which normally arise from rhombomeres 4 and 6, respectively. We found that the hyoid bone in kr/kr animals exhibited an accessory process on the greater horn (a third arch structure) most easily explained by ectopic development of a second arch structure (the hyoid lesser horn) in an area normally derived from the third arch.

REFERENCES

    1. Chavrier P.,
    2. Zerial M.,
    3. Lemaire P.,
    4. Almendral J.,
    5. Bravo R.,
    6. Charnay P.
    (1988) A gene encoding a protein with zinc fingers is activated during G0/G1 transition in cultured cells. EMBO J 7, 29–35
    OpenUrlPubMedWeb of Science
    1. Chisaka O.,
    2. Musci T. S.,
    3. Capecchi M. R.
    (1992). Developmental defects of the ear, cranial nerves and hindbrain resulting from targeted disruption of the mouse homeobox gene Hox-1.6. Nature 355, 516–520
    OpenUrlCrossRefPubMedWeb of Science
    1. Deol M. S.
    (1964) The abnormalities of the inner ear in kreisler mice. J. Embryol. Exp. Morph 12, 475–490
    OpenUrlPubMedWeb of Science
    1. Fraser S.,
    2. Keynes R.,
    3. Lumsden A.
    (1990) Segmentation in the chickembryo hindbrain is defined by cell lineage restrictions. Nature 344, 431–435
    OpenUrlCrossRefPubMed
    1. Frohman M. A.,
    2. Boyle M.,
    3. Martin G. R.
    (1990). Isolation of the mouse Hox-2.9 gene: analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm. Development 110, 589–607
    OpenUrlAbstract/FREE Full Text
    1. Frohman M. A.,
    2. Dush M. K.,
    3. Martin G. R.
    (1988) Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc. Natl. Acad. Sci. USA 85, 8998–9002
    OpenUrlAbstract/FREE Full Text
    1. Gaunt S. J.,
    2. Krumlauf R.,
    3. Duboule D.
    (1989). Mouse homeo-genes within a subfamily, Hox-1.4, −2.6 and -5.1, display similar anteroposterior domains of expression in the embryo, but show stage-and tissue-dependent differences in their regulation. Development 107, 131–141
    OpenUrlAbstract
    1. Graham A.,
    2. Papalopulu N.,
    3. Lorimer J.,
    4. McVey J. H.,
    5. Tuddenham E. G.,
    6. Krumlauf R.
    (1988). Characterization of a murine homeo box gene, Hox-2.6, related to the DrosophilaDeformed gene. Genes Dev 2, 1424–1438
    OpenUrlAbstract/FREE Full Text
    1. Guthrie S.,
    2. Muchamore I.,
    3. Kuroiwa A.,
    4. Marshall H.,
    5. Krumlauf R.,
    6. Lumsden A.
    (1992). Neuroectodermal autonomy of Hox-2.9 expression revealed by rhombomere transpositions. Nature 356, 157–159
    OpenUrlCrossRefPubMed
    1. Hertwig P.
    (1942) Sechs neue Mutationen bei der Hausmaus in ihrer Bedeutung fur allgemeine Vererbungsfragen. Z. Lehre 26, 1–21
    OpenUrl
    1. Hunt P.,
    2. Gulisano M.,
    3. Cook M.,
    4. Sham M. H.,
    5. Faiella A.,
    6. Wilkinson D.,
    7. Boncinelli E.,
    8. Krumlauf R.
    (1991) A distinct Hox code for the branchial region of the vertebrate head. Nature 353, 861–864
    OpenUrlCrossRefPubMedWeb of Science
    1. Hunt P.,
    2. Whiting J.,
    3. Muchamore I.,
    4. Marshall H.,
    5. Krumlauf R.
    (1991) Homeobox genes and models for patterning the hindbrain and branchial arches. Development 1, 187–196
    OpenUrlPubMed
    1. Hunt P.,
    2. Wilkinson D.,
    3. Krumlauf R.
    (1991) Patterning the vertebrate head: murine Hox 2 genes mark distinct subpopulations of premigratory and migrating cranial neural crest. Development 112, 43–50
    OpenUrlAbstract
    1. Justice M. J.,
    2. Bode V. C.
    (1986) Induction of new mutations in a mouse t -haplotype using ethylnitrosourea mutagenesis. Genet. Res 47, 187–192
    OpenUrlPubMedWeb of Science
    1. Kaan H. W.
    (1938) Further studies on the auditory vesicle and cartilaginous capsule of Amblystoma punctatum. J. Exp. Zool 78, 159–183
    OpenUrlCrossRefWeb of Science
    1. Keynes R.,
    2. Lumsden A.
    (1990) Segmentation and the origin of regional diversity in the vertebrate central nervous system. Neuron 2, 1–9
    OpenUrlPubMed
    1. LeDouarin N.
    (1980) Migration and differentiation of neural crest cells. Current Top. Dev. Biol 16, 32–86
    OpenUrl
    1. Lovett M.,
    2. Cheng Z. Y.,
    3. Lamela E. M.,
    4. Yokoi T.,
    5. Epstein C. J.
    (1987) Molecular markers for the agouti coat color locus of the mouse. Genetics 115, 747–754
    OpenUrlAbstract/FREE Full Text
    1. Lufkin T.,
    2. Dierich A.,
    3. LeMeur M.,
    4. Mark M.,
    5. Chambon P.
    (1991). Disruption of the Hox-1.6 homeobox gene results in defects in a region corresponding to its rostral domain of expression. Cell 66, 1105–1119
    OpenUrlCrossRefPubMedWeb of Science
    1. Lumsden A.,
    2. Keynes R.
    (1989) Segmental patterns of neuronal development in the chick hindbrain. Nature 337, 424–428
    OpenUrlCrossRefPubMedWeb of Science
    1. Lumsden A.,
    2. Sprawson N.,
    3. Graham A.
    (1991) Segmental origin and migration of neural crest cells in the hindbrain region of the chick embryo. Development 113, 1281–1291
    OpenUrlAbstract
    1. Mansour S. L.,
    2. Martin G. R.
    (1988) Four classes of mRNA are expressed from the mouse int-2 gene, a member of the FGF gene family. EMBO J 7, 2035–2041
    OpenUrlPubMedWeb of Science
    1. Mansour S. L.,
    2. Goddard J. M.,
    3. Capecchi M. R.
    (1993) Mice homozygous for a targeted disruption of the proto-oncogene Int-2 have developmental defects in the tail and inner ear. Development 117, 13–28
    OpenUrlAbstract/FREE Full Text
    1. McLeod M. J.
    (1980) Differential staining of cartilage and bone in whole mouse fetuses by alcian blue and alizarin red S. Teratology 22, 299–301
    OpenUrlCrossRefPubMedWeb of Science
    1. Morriss-Kay G. M.,
    2. Murphy P.,
    3. Hill R. E.,
    4. Davidson D. R.
    (1991). Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos. EMBO J 10, 2985–2995
    OpenUrlPubMedWeb of Science
    1. Morriss-Kay G. M.,
    2. Tan S.-S.
    (1987) Mapping cranial neural crest cell migration pathways in mammalian embryos. Trends Genet 3, 257–262
    OpenUrlCrossRef
    1. Murphy P.,
    2. Davidson D. R.,
    3. Hill R. E.
    (1989) Segment-specific expression of a homoeobox-containing gene in the mouse hindbrain. Nature 341, 156–159
    OpenUrlCrossRefPubMed
    1. Murphy P.,
    2. Hill R. E.
    (1991). Expression of the mouse labial -like homeobox-containing genes, Hox 2.9 and Hox 1.6 during segmentation of the hindbrain. Development 111, 61–74
    OpenUrlAbstract
    1. Noden D. M.
    (1973) An analysis of the migratory behavior of avian cephalic neural crest cells. Dev. Biol 42, 106–130
    OpenUrl
    1. Noden D. M.
    (1978) The control of avian cephalic neural crest cytodifferentiation. I. Skeletal and connective tissues. Dev. Biol 67, 296–312
    OpenUrlCrossRefPubMedWeb of Science
    1. Noden D. M.
    (1983) The role of the neural crest in patterning of avian cranial skeletal, connective and muscle tissues. Dev. Biol 96, 144–165
    OpenUrlCrossRefPubMedWeb of Science
    1. Noden D. M.
    (1988) Interactions and fates of avian craniofacial mesenchyme. Development 103, 121–140
    OpenUrlAbstract/FREE Full Text
    1. Papalopulu N.,
    2. Clarke J. D.,
    3. Bradley L.,
    4. Wilkinson D.,
    5. Krumlauf R.,
    6. Holder N.
    (1991) Retinoic acid causes abnormal development and segmental patterning of the anterior hindbrain in Xenopus embryos. Development 113, 1145–1158
    OpenUrlAbstract
    1. Represa J.,
    2. Leon Y.,
    3. Miner C.,
    4. Giraldez F.
    (1991) The int-2 proto-oncogene is responsible for induction of the inner ear. Nature 353, 561–563
    OpenUrlCrossRefPubMed
    1. Rinchik E. M.,
    2. Carpenter D. A.,
    3. Selby P. B.
    (1990) A strategy for fine-structure functional analysis of a 6-to 11-centimorgan region of mouse chromosome 7 by high-efficiency mutagenesis. Proc. Natl. Acad. Sci. USA 87, 896–900
    OpenUrlAbstract/FREE Full Text
    1. Sham M. H.,
    2. Hunt P.,
    3. Nonchev S.,
    4. Papalopulu N.,
    5. Graham A.,
    6. Boncinelli E.,
    7. Krumlauf R.
    (1992). Analysis of the murine Hox-2.7 gene: conserved alternative transcripts with differential distributions inthe nervous system and the potential for shared regulatory regions. EMBO J 11, 1825–1836
    OpenUrlPubMedWeb of Science
    1. Siracusa L. D.,
    2. Buchberg A. M.,
    3. Copeland N. G.,
    4. Jenkins N. A.
    (1989) Recombinant inbred strain and interspecific backcross analysis of molecular markers flanking the murine agouti coat color locus. Genetics 122, 669–679
    OpenUrlAbstract/FREE Full Text
    1. Siracusa L. D.,
    2. Russell L. B.,
    3. Jenkins N. A.,
    4. Copeland N. G.
    (1987) Allelic variation within the Emv-15 locus defines genomic sequences closely linked to the agouti locus on mouse chromosome 2. Genetics 117, 85–92
    OpenUrlAbstract/FREE Full Text
    1. Sundin O. H.,
    2. Busse H. G.,
    3. Rogers M. B.,
    4. Gudas L. J.,
    5. Eichele G.
    (1990). Region-specific expression in early chick and mouse embryos of Ghox-lab and Hox-1.6, vertebrate homeobox-containing genes related to Drosophila labial. Development 108, 47–58
    OpenUrlAbstract
    1. Sundin O. H.,
    2. Eichele G.
    (1990) A homeo domain protein reveals the metameric nature of the developing chick hindbrain. Genes Dev 4, 1267–1276
    OpenUrlAbstract/FREE Full Text
    1. Tuckett F.,
    2. Lim L.,
    3. Morriss-Kay G. M.
    (1985) The ontogenesis of cranial neuromeres in the rat embryo. I. A scanning electron microscope and kinetic study. J. Embryol. exp. Morph 87, 215–228
    OpenUrlPubMed
    1. Tuckett F.,
    2. Morriss-Kay G. M.
    (1985) The ontogenesis of cranial neuromeres in the rat embryo. II. A transmission electron microscope study. J. Embryol. exp. Morph 88, 231–247
    OpenUrlPubMed
    1. Wilkinson D. G.,
    2. Bhatt S.,
    3. Chavrier P.,
    4. Bravo R.,
    5. Charnay P.
    (1989) Segment-specific expression of a zinc-finger gene in the developing nervous system of the mouse. Nature 337, 461–464
    OpenUrlCrossRefPubMed
    1. Wilkinson D. G.,
    2. Bhatt S.,
    3. Cook M.,
    4. Boncinelli E.,
    5. Krumlauf R.
    (1989) Segmental expression of Hox-2 homoeobox-containing genes in the developing mouse hindbrain. Nature 341, 405–409
    OpenUrlCrossRefPubMed
    1. Wilkinson D. G.,
    2. Krumlauf R.
    (1990) Molecular approaches to the segmentation of the hindbrain. Trends Neurosci 13, 335–339
    OpenUrlCrossRefPubMedWeb of Science
    1. Wilkinson D. G.,
    2. Peters G.,
    3. Dickson C.,
    4. McMahon A. P.
    (1988) Expression of the FGF-related proto-oncogene int-2 during gastrulation and neurulation in the mouse. EMBO J 7, 691–695
    OpenUrlPubMedWeb of Science
    1. Yntema C. L.
    (1933) Experiments on the determination of the ear ectoderm of Amblystoma punctatum. J. Exp. Zool 65, 317–357
    OpenUrlCrossRefWeb of Science
    1. Yntema C. L.
    (1950) An analysis of induction of the ear from foreign ectoderm in the salamander embryo. J. Exp. Zool 113, 211–244
    OpenUrlCrossRef
    1. Zwilling E.
    (1941) The determination of the otic vesicle in Rana pipiens. J. Exp. Zool 86, 333–342
    OpenUrlCrossRef
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JOURNAL ARTICLES
Altered rhombomere-specific gene expression and hyoid bone differentiation in the mouse segmentation mutant, kreisler (kr)
M.A. Frohman, G.R. Martin, S.P. Cordes, L.P. Halamek, G.S. Barsh
Development 1993 117: 925-936;
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