Advertisement
JOURNAL ARTICLES
Loss of Hox-A1 (Hox-1.6) function results in the reorganization of the murine hindbrain
E.M. Carpenter, J.M. Goddard, O. Chisaka, N.R. Manley, M.R. Capecchi
Development 1993 118: 1063-1075;

Summary

Targeted disruption of the murine hox-A1 gene results in severe defects in the formation of the hindbrain and associated cranial ganglia and nerves. Carbocyanine dye injections were used to trace afferent and efferent projections to and from the hindbrain in hox-A1-/hox-A1- mutant mice. Defects were observed in the position of efferent neurons in the hindbrain and in their projection patterns. In situ hybridization was used to analyze the transcription pattern of genes expressed within specific rhombomeres. Krox-20, int-2 (fgf-3), and hox-B1 all display aberrant patterns of expression in hox-A1- mutant embryos. The observed morphological and molecular defects suggest that there are changes in the formation of the hindbrain extending from rhombomere 3 through rhombomere 8 including the absence of rhombomere 5. Also, motor neurons identified by their axon projection patterns which would normally be present in the missing rhombomere appear to be respecified to or migrate into adjacent rhombomeres, suggesting a role for hox-A1 in the specification of cell identity and/or cell migration in the hindbrain.

Reference

    1. Bally-Cuif L.,
    2. Alvarado-Mallart R.-M.,
    3. Darnell D. K.,
    4. Wassef M.
    (1992) Relationship between Wnt-1 and En-2 expression domains during early development of normal and ectopic met-mesencephalon. Development 115, 999–1009
    OpenUrlAbstract
    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
    OpenUrlCrossRefPubMed
    1. Duboule D.,
    2. Dolle P.
    (1989) The structural and functional organization of the murine Hox gene family resembles that of Drosophila homeotic genes. EMBO J 8, 1497–1505
    OpenUrlPubMedWeb of Science
    1. Fraser S.,
    2. Keynes R.,
    3. Lumsden A.
    (1990) Segmentation in the chick embryo 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. Graham A.,
    2. Papalopulu N.,
    3. Krumlauf R.
    (1989) The murine and Drosophila homeobox gene complexes have common features of organization and expression. Cell 57, 367–378
    OpenUrlCrossRefPubMedWeb of Science
    1. Guthrie S.,
    2. Lumsden A.
    (1991) Formation and regeneration of rhombomere boundaries in the developing chick hindbrain. Development 112, 221–229
    OpenUrlAbstract
    1. Harland R. M.
    (1991) In situ hybridization: an improved whole mount method for Xenopus embryos. Meth. Cell Biol 36, 685–695
    OpenUrlPubMed
    1. Hunt P.,
    2. Whiting J.,
    3. Nonchev S.,
    4. Sham M.,
    5. Marshall H.,
    6. Graham A.,
    7. Cook M.,
    8. Allemann R.,
    9. Rigby P. W. J.,
    10. Gulisano M.,
    11. Faiella A.,
    12. Boncinelli E.,
    13. Krumlauf R.
    (1991) The branchial Hox code and its implications for gene regulation, patterning of the nervous system and head evolution. Development 2, 63–77
    OpenUrlPubMed
    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.
    (1990) The cellular basis of segmentation in the developing hindbrain. Trends Neurosci 13, 329–335
    OpenUrlCrossRefPubMedWeb of Science
    1. Lumsden A.,
    2. Keynes R.
    (1989) Segmental patterns of neuronal development in the chick hindbrain. Nature 337, 424–428
    OpenUrlCrossRefPubMed
    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. Thomas K. R.,
    3. Deng C. X.,
    4. Capecchi M. R.
    (1990) Introduction of a lac-Z reporter gene into the mouse int-2 locus by homologous recombination. Proc. Natl. Acad. Sci. USA 87, 7688–7692
    OpenUrlAbstract/FREE Full Text
    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. Marshall H.,
    2. Nonchev S.,
    3. Sham M. H.,
    4. Muchamore I.,
    5. Lumsden A.,
    6. Krumlauf R.
    (1992) Retinoic acid alters hindbrain Hox code and induces transformation of rhombomeres 2/3 into a 4/5 identity. Nature 360, 737–741
    OpenUrlCrossRefPubMed
    1. McMahon A. P.,
    2. Bradley A.
    (1990) The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell 62, 1073–1085
    OpenUrlCrossRefPubMedWeb of Science
    1. Murphy P.,
    2. Davidson D. R.,
    3. Hill R. E.
    (1989) Segment-specific expression of a homeobox-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. Scott M. P.
    (1992) Vertebrate homeobox gene nomenclature. Cell 71, 551–553
    OpenUrlCrossRefPubMedWeb of Science
    1. Serbedzija G. N.,
    2. Bronner-Fraser M.,
    3. Fraser S. E.
    (1992) Vital dye analysis of cranial neural crest migration in the mouse embryo. Development 116, 297–307
    OpenUrlAbstract/FREE Full Text
    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. 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 homeobox-containing genes in the developing mouse hindbrain. Nature 341, 405–409
    OpenUrlCrossRefPubMed
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Loss of Hox-A1 (Hox-1.6) function results in the reorganization of the murine hindbrain
E.M. Carpenter, J.M. Goddard, O. Chisaka, N.R. Manley, M.R. Capecchi
Development 1993 118: 1063-1075;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

Kathryn Virginia Anderson (1952-2020)

Developmental geneticist Kathryn Anderson passed away at home on 30 November 2020. Tamara Caspary, a former postdoc and friend, remembers Kathryn and her remarkable contribution to developmental biology.

Zooming into 2021

In a new Editorial, Editor-in-Chief James Briscoe and Executive Editor Katherine Brown reflect on the triumphs and tribulations of the last 12 months, and look towards a hopefully calmer and more predictable year.

Read & Publish participation extends worldwide

Over 60 institutions in 12 countries are now participating in our Read & Publish initiative. Here, James Briscoe explains what this means for his institution, The Francis Crick Institute. Find out more and view our full list of participating institutions.

Upcoming special issues

Imaging Development, Stem Cells and Regeneration
Submission deadline: 30 March 2021
Publication: mid-2021

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

Both special issues welcome Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Sign up to join our next session:

10 February
Time: 13:00 (GMT)
Chaired by: preLights