Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Special issues
    • Subject collections
    • Sign up for alerts
  • About us
    • About Development
    • About the Node
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Journal Meetings
    • Workshops
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contacts
    • Contacts
    • Subscriptions
    • Feedback
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

User menu

  • Log in
  • Log out

Search

  • Advanced search
Development
  • COB
    • About The Company of Biologists
    • Development
    • Journal of Cell Science
    • Journal of Experimental Biology
    • Disease Models & Mechanisms
    • Biology Open

supporting biologistsinspiring biology

Development

  • Log in
Advanced search

RSS  Twitter  Facebook  YouTube 

  • Home
  • Articles
    • Accepted manuscripts
    • Issue in progress
    • Latest complete issue
    • Issue archive
    • Archive by article type
    • Special issues
    • Subject collections
    • Sign up for alerts
  • About us
    • About Development
    • About the Node
    • Editors and Board
    • Editor biographies
    • Travelling Fellowships
    • Grants and funding
    • Journal Meetings
    • Workshops
    • The Company of Biologists
    • Journal news
  • For authors
    • Submit a manuscript
    • Aims and scope
    • Presubmission enquiries
    • Article types
    • Manuscript preparation
    • Cover suggestions
    • Editorial process
    • Promoting your paper
    • Open Access
    • Biology Open transfer
  • Journal info
    • Journal policies
    • Rights and permissions
    • Media policies
    • Reviewer guide
    • Sign up for alerts
  • Contacts
    • Contacts
    • Subscriptions
    • Feedback
JOURNAL ARTICLES
Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse
J.R. Barrow, H.S. Stadler, M.R. Capecchi
Development 2000 127: 933-944;
J.R. Barrow
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
H.S. Stadler
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M.R. Capecchi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & metrics
  • PDF
Loading

Summary

Early in its development, the vertebrate hindbrain is transiently subdivided into a series of compartments called rhombomeres. Genes have been identified whose expression patterns distinguish these cellular compartments. Two of these genes, Hoxa1 and Hoxa2, have been shown to be required for proper patterning of the early mouse hindbrain and the associated neural crest. To determine the extent to which these two genes function together to pattern the hindbrain, we generated mice simultaneously mutant at both loci. The hindbrain patterning defects were analyzed in embryos individually mutant for Hoxa1 and Hoxa2 in greater detail and extended to embryos mutant for both genes. From these data a model is proposed to describe how Hoxa1, Hoxa2, Hoxb1, Krox20 (Egr2) and kreisler function together to pattern the early mouse hindbrain. Critical to the model is the demonstration that Hoxa1 activity is required to set the anterior limit of Hoxb1 expression at the presumptive r3/4 rhombomere boundary. Failure to express Hoxb1 to this boundary in Hoxa1 mutant embryos initiates a cascade of gene misexpressions that result in misspecification of the hindbrain compartments from r2 through r5. Subsequent to misspecification of the hindbrain compartments, ectopic induction of apoptosis appears to be used to regulate the aberrant size of the misspecified rhombomeres.

REFERENCES

    1. Albano R. M.,
    2. Arkell R.,
    3. Beddington R. S.,
    4. Smith J. C.
    (1994) Expression of inhibin subunits and follistatin during postimplantation mouse development: decidual expression of activin and expession of folistatin in primitive streak, somites and hindbrain. Development 120, 803–813
    OpenUrlAbstract
    1. Barrow J. R.,
    2. Capecchi M. R.
    (1996) Targeted disruption of the hoxb-2 locus in mice interferes with expression of hoxb-1 and hoxb-4. Development 122, 3817–3828
    OpenUrlAbstract
    1. Barrow J. R.,
    2. Capecchi M. R.
    (1999) Compensatory defects associated with mutations in Hoxa1 restore normal palatogenesis to Hoxa2 mutants. Development 126, 5011–5026
    OpenUrlAbstract
    1. Carpenter E. M.,
    2. Goddard J. M.,
    3. Chisaka O.,
    4. Manley N. R.,
    5. Capecchi M. R.
    (1993). Loss of Hox-A1 (Hox-1.6) function results in the reorganization of the murine hindbrain. Development 118, 1063–1075
    OpenUrlAbstract/FREE Full Text
    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. 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. Frohman M. A.,
    2. Martin G. R.,
    3. Cordes S. P.,
    4. Halamek L. P.,
    5. Barsh G. S.
    (1993) Altered rhombomere-specific gene expression and hyoid bone differentiation in the mouse segmentation mutant, kreisler (kr). Development 117, 925–936
    OpenUrlAbstract
    1. Gavalas A.,
    2. Davenne M.,
    3. Lumsden A.,
    4. Chambon P.,
    5. Rijli F. M.
    (1997) Control of axon guidance and rostral hindbrain patterning by Hoxa2. Development 124, 3693–3702
    OpenUrlAbstract
    1. Gavalas A.,
    2. Studer M.,
    3. Lumsden A.,
    4. Rijli F. M.,
    5. Krumlauf R.,
    6. Chambon P.
    (1998) Hoxa1 and Hoxb1 synergize in patterning the hindbrain, cranial nerves and second pharyngeal arch. Development 125, 1123–1136
    OpenUrlAbstract
    1. Gendron-Maguire M.,
    2. Mallo M.,
    3. Zhang M.,
    4. Gridley T.
    (1993) Hoxa-2 mutant mice exhibit homeotic transformation of skeletal elements derived from cranial neural crest. Cell 75, 1317–1331
    OpenUrlCrossRefPubMedWeb of Science
    1. Gilardi-Hebenstreit P.,
    2. Nieto M. A.,
    3. Frain M.,
    4. Mattei M.-G.,
    5. Chestier A.,
    6. Wilkinson D. G.,
    7. Charnay P.
    (1992) An Eph -related receptor protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain. Oncogene 7, 2499–2506
    OpenUrlPubMedWeb of Science
    1. Goddard J. M.,
    2. Rossel M.,
    3. Manley N. R.,
    4. Capecchi M. R.
    (1996) Mice with targeted disruption of Hoxb-1 fail to form the motor nucleus of the VIIth nerve. Development 122, 3217–3228
    OpenUrlAbstract
    1. Godwin A.R.,
    2. Stadler H. S.,
    3. Nakamura K.,
    4. Capecchi M. R.
    (1998) Detection of targeted GFP-Hox gene fusions during mouse embryogenesis. Proc. Natl. Acad. Sci. USA 95, 13042–13047
    OpenUrlAbstract/FREE Full Text
    1. Graham A.,
    2. Lumsden A.
    (1996) Interactions between rhombomeres modulate Krox20 and follistatin expression in the chick embryo hindbrain. Development 122, 473–480
    OpenUrlAbstract
    1. Helmbacher F.,
    2. Pujades C.,
    3. Desmarquet C.,
    4. Frain M.,
    5. Rijli F. M.,
    6. Chambon P.,
    7. Charnay P.
    (1998) Hoxa1 and Krox20 synergize to control the development of rhombomere 3. Development 125, 4739–4748
    OpenUrlAbstract
    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
    OpenUrlCrossRefPubMed
    1. Hunt P.,
    2. Whiting J.,
    3. Nonchev S.,
    4. Sham M.-H.,
    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
    1. Irving C.,
    2. Nieto M. A.,
    3. DasGupta R.,
    4. Charnay P.,
    5. Wilkinson D. G.
    (1996) Progressive spatial restriction of Sek-1 and Krox20 gene expression during hindbrain segmentation. Dev. Biol 173, 26–38
    OpenUrlCrossRefPubMedWeb of Science
    1. Köntges G.,
    2. Lumsden A.
    (1996) Rhombencephalic neural crest segmentation is preserved throughout craniofacial ontogeny. Development 122, 3229–3242
    OpenUrlAbstract
    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
    OpenUrlCrossRefPubMed
    1. Manley N. R.,
    2. Capecchi M. R.
    (1995) The role of hoxa-3 in mouse thymus and thyroid development. Development 121, 1989–2003
    OpenUrlAbstract
    1. Mark M.,
    2. Lufkin T.,
    3. Vonesch J.-L.,
    4. Ruberte E.,
    5. Olivo J.-C.,
    6. Dolle P.,
    7. Gorry P.,
    8. Lumsden A.,
    9. Chambon P.
    (1993) Two rhombomeres are altered in Hoxa-1 mutant mice. Development 119, 319–338
    OpenUrlAbstract
    1. McGinnis W.,
    2. Krumlauf R.
    (1992) Homeobox genes and axial patterning. Cell 68, 283–302
    OpenUrlCrossRefPubMedWeb of Science
    1. McKay I. J.,
    2. Muchamore I.,
    3. Krumlauf R.,
    4. Maden M.,
    5. Lumsden A.,
    6. Lewis J.
    (1994) The kreisler mouse: a hindbrain segmentation mutant that lacks two rhombomeres. Development 121, 2199–2211
    OpenUrlAbstract
    1. Meyer D.,
    2. Yamaai T.,
    3. Garratt A.,
    4. Riethmacher-Sonnenberg E.,
    5. Kane D.,
    6. Theill L. E.,
    7. Birchmeier C.
    (1997) Isoform-specific expression and function of neuregulin. Development 124, 3575–3586
    OpenUrlAbstract
    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. Nonchev S.,
    2. Vesque C.,
    3. Maconochie M.,
    4. Seitanidou T.,
    5. Ariza-McNaughton L.,
    6. Frain M.,
    7. Marshall H.,
    8. Sham M. H.,
    9. Krumlauf R.,
    10. Charnay P.
    (1996) Segmental expression of Hoxa-2 in the hindbrain is directly regulated by Krox 20. Development 122, 543–554
    OpenUrlAbstract
    1. Rijli F. M.,
    2. Mark M.,
    3. Lakkaraju S.,
    4. Dierich A.,
    5. Dolle P.,
    6. Chambon P.
    (1993) A homeotic transformation is generated in the rostral branchial region of the head by disruption of Hoxa-2, which acts as a selector gene. Cell 75, 1333–1349
    OpenUrlCrossRefPubMedWeb of Science
    1. Rossel M.,
    2. Capecchi M. R.
    (1999) Mice mutant for both Hoxa1 and Hoxb1 show extensive remodeling of the hindbrain and defects in craniofacial development. Development 126, 5027–5040
    OpenUrlAbstract
    1. Schneider-Maunoury S.,
    2. Topilko P.,
    3. Seitanidou T.,
    4. Levi G.,
    5. Cohen-Tannoudji M.,
    6. Pournin S.,
    7. Babinet C.,
    8. Charnay P.
    (1993) Disruption of Krox20 results in alteration of rhombomeres 3 and 5 in the developing hindbrain. Cell 75, 1199–1214
    OpenUrlCrossRefPubMedWeb of Science
    1. Schwenk F.,
    2. Baron U.,
    3. Rajewsky K.
    (1995) A cre -transgenic mouse strain for the ubiquitous deletion of loxP -flanked gene segments including deletion in germ cells. Nucleic Acids Res 23, 5080–5081
    OpenUrlFREE Full Text
    1. Seitanidou T.,
    2. Schneider-Maunoury S.,
    3. Desmarquet C.,
    4. Wilkinson D. G.,
    5. Charnay P.
    (1997) Krox20 is a key regulator of rhombomere-specific gene expression in the developing hindbrain. Mech. Dev 65, 31–42
    OpenUrlCrossRefPubMedWeb of Science
    1. Sham M. H.,
    2. Vesque C.,
    3. Nonchev S.,
    4. Marshall H.,
    5. Frain M.,
    6. Gupta R. D.,
    7. Whiting J.,
    8. Wilkinson D.,
    9. Charnay P.,
    10. Krumlauf R.
    (1993). The zinc finger gene Krox20 regulates HoxB2 (Hox2.8) during hindbrain segmentation. Cell 72, 183–196
    OpenUrlCrossRefPubMedWeb of Science
    1. Studer M.,
    2. Gavalas A.,
    3. Marshall H.,
    4. Ariza-McNaughton L.,
    5. Rijli F. M.,
    6. Chambon P.,
    7. Krumlauf R.
    (1998) Genetic interactions between Hoxa1 and Hoxb1 reveal new roles in regulation of early hindbrain patterning. Development 125, 1025–1036
    OpenUrlAbstract
    1. Studer M.,
    2. Lumsden A.,
    3. Ariza-McNaughton L.,
    4. Bradley A.,
    5. Krumlauf R.
    (1996) Altered segmental identity and abnormal migration of motor neurons in mice lacking Hoxb-1. Nature 384, 630–634
    OpenUrlCrossRefPubMed
    1. Trainor P. A.,
    2. Tam P. P.
    (1995) Cranial paraxial mesoderm and neural crest cells of the mouse embryo: co-distribution in the craniofacial mesenchyme but distinct segregation in branchial arches. Development 121, 2569–2582
    OpenUrlAbstract
    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. Zhang M.,
    2. Kim H.-J.,
    3. Marshall H.,
    4. Gendron-Maguire M.,
    5. Lucas D. A.,
    6. Baron A.,
    7. Gudas L. J.,
    8. Gridley T.,
    9. Krumlauf R.,
    10. Grippo J. F.
    (1994) Ectopic Hoxa-1 induces rhombomere transformation in the mouse hindbrain. Development 120, 2431–2442
    OpenUrlAbstract/FREE Full Text
Previous ArticleNext Article
Back to top
Previous ArticleNext Article

This Issue

 Download PDF

Email

Thank you for your interest in spreading the word on Development.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse
(Your Name) has sent you a message from Development
(Your Name) thought you would like to see the Development web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
JOURNAL ARTICLES
Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse
J.R. Barrow, H.S. Stadler, M.R. Capecchi
Development 2000 127: 933-944;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
JOURNAL ARTICLES
Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse
J.R. Barrow, H.S. Stadler, M.R. Capecchi
Development 2000 127: 933-944;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Alerts

Please log in to add an alert for this article.

Sign in to email alerts with your email address

Article navigation

  • Top
  • Article
  • Info & metrics
  • PDF

Related articles

Cited by...

More in this TOC section

  • Morphogenetic cell movements in the middle region of the dermomyotome dorsomedial lip associated with patterning and growth of the primary epaxial myotome
  • Germline and developmental roles of the nuclear transport factor importin (α)3 in C. elegans
  • Monofocal origin of telencephalic oligodendrocytes in the anterior entopeduncular area of the chick embryo
Show more JOURNAL ARTICLES

Similar articles

Other journals from The Company of Biologists

Journal of Cell Science

Journal of Experimental Biology

Disease Models & Mechanisms

Biology Open

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

Articles

  • Accepted manuscripts
  • Issue in progress
  • Latest complete issue
  • Issue archive
  • Archive by article type
  • Special issues
  • Subject collections
  • Sign up for alerts

About us

  • About Development
  • About the Node
  • Editors and board
  • Editor biographies
  • Travelling Fellowships
  • Grants and funding
  • Journal Meetings
  • Workshops
  • The Company of Biologists

For authors

  • Submit a manuscript
  • Aims and scope
  • Presubmission enquiries
  • Article types
  • Manuscript preparation
  • Cover suggestions
  • Editorial process
  • Promoting your paper
  • Open Access
  • Biology Open transfer

Journal info

  • Journal policies
  • Rights and permissions
  • Media policies
  • Reviewer guide
  • Sign up for alerts

Contact

  • Contact Development
  • Subscriptions
  • Advertising
  • Feedback

 Twitter   YouTube   LinkedIn

© 2021   The Company of Biologists Ltd   Registered Charity 277992