Advertisement
JOURNAL ARTICLES
The caudal limit of Otx2 gene expression as a marker of the midbrain/hindbrain boundary: a study using in situ hybridisation and chick/quail homotopic grafts
S. Millet, E. Bloch-Gallego, A. Simeone, R.M. Alvarado-Mallart
Development 1996 122: 3785-3797;

Summary

Segmentation of the neural tube has been clearly shown in the forebrain and caudal hindbrain but has never been demonstrated within the midbrain/hindbrain domain. Since the homeobox-containing gene Otx2 has a caudal limit of expression in this region, we examined, mainly in chick embryos, the possibility that this limit could represent an interneuromeric boundary separating either two cerebellar domains or the mesencephalic and cerebellar primordia. In situ hybridisation with chick or mouse Otx2 probes showed the existence of a transient Otx2-negative area in the caudal mesencephalic vesicle, between stages HH10 and HH17/18 in chick, and at embryonic day 9.5 in mice. The first post-mitotic neurons of the mesencephalon sensu stricto, as labelled with an anti-beta-tubulin antibody, overlay the Otx2-positive neuroepithelium with a perfect match of the caudal limits of these two markers at all embryonic stages analysed (until stage HH20). Chick/quail homotopic grafts of various portions of the midbrain/hindbrain domain have shown that the progeny of the cells located in the caudal mesencephalic vesicle at stage HH10 are found within the rhombomere 1 as early as stage HH14. Furthermore, our results indicate that the cells forming the HH20 constriction (coinciding with the caudal Otx2 limit) are the progeny of those located at the caudal Otx2 limit at stage HH10 (within the mesencephalic vesicle). As a result, the Otx2-positive portion of the HH10 mesencephalic vesicle gives rise to the HH20 mesencephalon, while the Otx2-negative portion gives rise to the HH20 rostral rhombomere 1. Long-survival analysis allowing the recognition of the various grisea of the chimeric brains strongly supports the view that, as early as stage HH10, the caudal limit of Otx2 expression separates mesencephalic from isthmo/cerebellar territories. Finally, this study revealed unexpected rostrocaudal morphogenetic movements taking place between stages HH10 and HH16 in the mediodorsal part of the caudal Otx2-positive domain.

Reference

    1. Acampora D.,
    2. Mazan S.,
    3. Lallemand Y.,
    4. Avantaggiato V.,
    5. Maury M.,
    6. Simeone A.,
    7. Brûlet P.
    (1995) Forebrain and hindbrain regions are deleted in Otx2 /mutants due to a defective anterior neurectoderm specification during gastrulation. Development 121, 3279–3290
    OpenUrlAbstract
    1. Alvarado-Mallart R.-M.,
    2. Sotelo C.
    (1984) Homotopic and heterotopic transplantations of quail tectal primordia in chick embryos: organization of the retino-tectal projections in the chimeric embryos. Dev. Biol 103, 378–398
    OpenUrlCrossRefPubMed
    1. Alvarez Otero R.,
    2. Sotelo C.,
    3. Alvarado-Mallart R.-M.
    (1993) Chick/quail chimeras with partial cerebellar grafts: an analysis of the origin and migration of cerebellar cells. J. Comp. Neurol 333, 597–615
    OpenUrlCrossRefPubMedWeb of Science
    1. Ang S. L.,
    2. Jin O.,
    3. Rhinn M.,
    4. Daigle N.,
    5. Stevenson L.,
    6. Rossant J.
    (1996) A targeted mouse Otx2 mutation leads to devere defects in gastrulation and formation of axial mesoderm and to deletion of rostral brain. Development 122, 243–252
    OpenUrlAbstract
    1. Bally-Cuif L.,
    2. Wassef M.
    (1994) Ectopic induction and reorganization of Wnt-1 expression in quail/chick chimeras. Development 120, 3379–3394
    OpenUrlAbstract
    1. Bally-Cuif L.,
    2. Wassef M.
    (1995) Determination events in the nervous system of the vertebrate embryo. Cur. Op. in Gen. Dev 5, 450–458
    OpenUrlCrossRefPubMedWeb of Science
    1. Bally-Cuif L.,
    2. Cholley B.,
    3. Wassef M.
    (1995) Involvement of Wnt-1 in the formation of the mes-metencephalic boundary. Mech. Dev 53, 23–34
    OpenUrlCrossRefPubMedWeb of Science
    1. Bulfone A.,
    2. Puelles L.,
    3. Porteus M. H.,
    4. Frohman M. A.,
    5. Martin G. R.,
    6. Rubenstein J. L. R.
    (1993). Spacially restricted expression of Dlx-1, Dlx-2 (Tes-1), Gbx-2, and Wnt-3 in the embryonic day 12.5 mouse forebrain defines potential transverse and longitudinal segmental bounderies. J. Neurosci 13, 3155–3172
    OpenUrlAbstract
    1. Chedotal A.,
    2. Pourquie O.,
    3. Sotelo C.
    (1995) Initial tract formation in the brain of the chick embryo: selective expression of the BEN/SC1/DM-GRASP cell adhesion molecule. Eur. J. Neurosci 7, 198–212
    OpenUrlCrossRefPubMedWeb of Science
    1. Cohen S. M.,
    2. Jurgens G.
    (1991) Drosophila headlines. Trends Genet 7, 267–272
    OpenUrlPubMedWeb of Science
    1. Easter S. S.,
    2. Ross L. S.,
    3. Frankfurter A.
    (1993) Initial tract formation in the mouse brain. J. Neurosci 13, 285–299
    OpenUrlAbstract
    1. Figdor M. C.,
    2. Stern C. D.
    (1993) Segmental organization of embryonic diencephalon. Nature 363, 630–634
    OpenUrlCrossRefPubMed
    1. Finkelstein R.,
    2. Perrimon N.
    (1990) The orthodenticle gene is regulated by bicoid and torso and specifies Drosophila head development. Nature 346, 485–488
    OpenUrlCrossRefPubMed
    1. Frantz G. D.,
    2. Welmann J. M.,
    3. Levin M. E.,
    4. McConnell S. K.
    (1994) OTX1 and OTX2 define layers and regions in developing cerebral cortex and cerebellum. Dev. Neurosci 14, 5725–5740
    OpenUrl
    1. Fraser S.,
    2. Keynes R.,
    3. Lumsden A.
    (1990) Segmentation in the chick embryo hindbrain is defined by cell lineage restriction. Nature 344, 431–435
    OpenUrlCrossRefPubMed
    1. Goldberg S.
    (1974) Studies on the mechanics of development of the visual pathways in the chick embryos. Dev. Biol 36, 24–43
    OpenUrlCrossRefPubMedWeb of Science
    1. Hallonet M. E. R.,
    2. Teillet M.-A.,
    3. Le Douarin N. M.
    (1990) A new approach to the development of the cerebellum provided by the quail-chick marker system. Development 108, 19–31
    OpenUrlAbstract
    1. Hallonet M. E. R.,
    2. Le Douarin N. M.
    (1993) Tracing neuroepithelialcells in the mesencephalic and metencephalic alar plates during cerebellar ontogeny in Quail-Chick chimaeras. Eur. J. Neurosci 5, 1145–1155
    OpenUrlCrossRefPubMedWeb of Science
    1. Hamburger V.,
    2. Hamilton H. L.
    (1951) A series of normal stages in the development of the chick embryo. J. Morphol 88, 49–92
    OpenUrlCrossRefWeb of Science
    1. Herrup K.,
    2. Wilczynski S. L.
    (1982) Cerebellar cell degeneration in the leaner mutant mouse. Neurosci 7, 2185–2196
    OpenUrlCrossRefPubMedWeb of Science
    1. Hirth F.,
    2. Therianos S.,
    3. Loop T.,
    4. Gehring W. J.,
    5. Reichert H.,
    6. Furukubo-Tokunaga K.
    (1995) Developmental defects in brain segmentation caused by mutations of the homeobox genes orthodenticle and empty spinacles in Drosophila. Neuron 15, 769–778
    OpenUrlCrossRefPubMedWeb of Science
    1. Le Douarin N. M.
    (1969) Particularites du noyau interphasique chez la caille japonaise (Coturnix coturnix japonica). Utilisation de ces particularites comme marquage biologique dans les recherches. Bull. Biol. Fr. Belg 103, 435–452
    OpenUrlPubMed
    1. Marin F.,
    2. Puelles L.
    (1994) Patterning of the embryonic avian midbrain after experimental inversions: a polarizing activity from the isthmus. Dev. Biol 163, 19–37
    OpenUrlCrossRefPubMedWeb of Science
    1. Marin F.,
    2. Puelles L.
    (1995) Morphological fate of rhombomere in quail/chick chimeras: a segmental analysis of hindbrain nuclei. Eur. J. Neurosci 7, 1714–1738
    OpenUrlCrossRefPubMedWeb of Science
    1. Martinez S.,
    2. Alvarado-Mallart R.-M.
    (1989) Rostral cerebellum originates from caudal portion of the so-called ‘mesencephalic’ vesicle: a study using chick/quail chimeras. Eur. J. Neurosci 1, 549–560
    OpenUrlCrossRefPubMedWeb of Science
    1. Martinez S.,
    2. Geijo E.,
    3. Sanchez-Vives M. V.,
    4. Puelles L.,
    5. Gallego R.
    (1992) Reduced junctional permeability at interrhombomeric boundaries. Development 116, 1069–1076
    OpenUrlAbstract
    1. Martinez S.,
    2. Geijo E.,
    3. Sanchez-Vives M.,
    4. Puelles L.,
    5. Gallego R.
    (1993) Diencephalic intersegmental boundaries in the chick: boundary cells and junctional properties. Eur. J. Neurosci. Supplement 6, 112–.
    OpenUrl
    1. Matsuo I.,
    2. Kuratani S.,
    3. Kimura C.,
    4. Takeda N.,
    5. Aizawa S.
    (1995) Mouse Otx2 functions in the formation and patterning of rostral head. Genes Dev 9, 2646–2658
    OpenUrlAbstract/FREE Full Text
    1. McGinnis W.,
    2. Krumlauf R.
    (1992) Homeobox genes and axial patterning. Cell 68, 283–302
    OpenUrlCrossRefPubMedWeb of Science
    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. Millen K. J.,
    2. Hui C.-C.,
    3. Joyner A. L.
    (1995) A role for En-2 and other murine homologues of Drosophila segment polarity genes in regulating positional information in the developing cerebellum. Development 121, 3935–3945
    OpenUrlAbstract
    1. Millet S.,
    2. Bloch-Gallego E.,
    3. Simeone A.,
    4. Alvarado-Mallart R.-M.
    (1994) Dual expression of the Otx2 homeobox-containing gene during the development of the chick brain. Eur. J. Neurosci. Supplement 7, 78–.
    OpenUrl
    1. Moody S. A.,
    2. Quigg M. S.,
    3. Frankfurter A.
    (1989) Development of the peripheral trigeminal system in the chick revealed by an isotype-specific anti--tubulin monoclonal antibody. J. Comp. Neurol 279, 567–580
    OpenUrlCrossRefPubMedWeb of Science
    1. Puelles L.,
    2. Martinez-de-la-Torre M.
    (1987) Autoradiographic and Golgi study on the early development of n. isthmi principalis and adjacent grisea in the chick embryo: a tridimentional view point. Anat. Embryol 176, 19–34
    OpenUrlCrossRefPubMed
    1. Puelles L.,
    2. Rubenstein L. R.
    (1993) Expression patterns of homeobox and other putative regulatory genes in the embryonic mouse forebrain suggest a neuromeric organization. Trends Neurosci 16, 472–478
    OpenUrlCrossRefPubMedWeb of Science
    1. Ross M. E.,
    2. Fletcher C.,
    3. Mason C. A.,
    4. Hatten M. E.,
    5. Heintz N.
    (1990) Meander tail reveals a discute developmental unit in the mouse cerebellum. Proc. Natl. Acad. Sci. USA 87, 4189–4192
    OpenUrlAbstract/FREE Full Text
    1. Royet J.,
    2. Finkelstein R.
    (1995) Pattern formation in Drosophila head development: the role of the orthodenticle homeobox gene. Development 121, 3561–3572
    OpenUrlAbstract
    1. Rubenstein J. L. R.,
    2. Martinez S.,
    3. Shimamura K.,
    4. Puelles L.
    (1994) The embryonic vertebrate forebrain: the prosomeric model. Science 266, 578–580
    OpenUrlFREE Full Text
    1. Senut M. C.,
    2. Alvarado-Mallart R.-M.
    (1987) Cytodifferentiation of quail tectal primordium transplanted homotopically into the chick embryo. Dev. Brain Res 32, 187–205
    OpenUrlCrossRef
    1. Shepherd I. T.,
    2. Taylor J. S. H.
    (1995) Early development of efferent projections from the chick tectum. J. Comp. Neurol 354, 501–510
    OpenUrlCrossRefPubMedWeb of Science
    1. Shimamura K.,
    2. Takeichi M.
    (1992) Local and transient expression of E-cadherin involved in mouse embryonic brain morphogenesis. Development 116, 1011–1019
    OpenUrlAbstract/FREE Full Text
    1. Shimamura K.,
    2. Hirano S.,
    3. McMahon A. P.,
    4. Takeichi M.
    (1994) Wnt-1-dependent regulation of local E-cadherin and N-catenin expression in the embryonic mouse brain. Development 120, 2225–2234
    OpenUrlAbstract
    1. Simeone A.,
    2. Acampora D.,
    3. Massino G.,
    4. Stornaiuolo A.,
    5. Boncinelli E.
    (1992) Nested expression domains of four homeobox genes in developing rostral brain. Nature 358, 687–690
    OpenUrlCrossRefPubMed
    1. Simeone A.,
    2. Acampora D.,
    3. Mallamaci A.,
    4. Stornaiuolo A.,
    5. D'Apice M.-R.,
    6. Nigro V.,
    7. Boncinelli E.
    (1993) A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulation mouse embryo. EMBO J 12, 2735–2747
    OpenUrlPubMedWeb of Science
    1. Sternberger L. A.,
    2. Hardy P. H., Jr.,
    3. Cuculis J. J.,
    4. Meyer H. G.
    (1970) The unlabeled antibody method of immunohistochemistry. Preparation and properties of soluble antigen complex and its use in identification of spirochetes. J. Histochem. Cytochem 18, 315–333
    OpenUrlAbstract/FREE Full Text
    1. Thomas K. R.,
    2. Capecchi M. R.
    (1990) Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development. Nature 346, 847–850
    OpenUrlCrossRefPubMed
    1. Wilkinson D. G.
    (1993) Molecular mechanisms of segmental patterning in the vertebrate hindbrain and neural crest. BioEssays 15, 499–505
    OpenUrlCrossRefPubMedWeb of Science
    1. Wurst W.,
    2. Auerbach A. B.,
    3. Joyner A. L.
    (1994) Multiple developmental defects in Engrailed-1 mutant mice: an early mid-hindbrain deletion and patterning defects in forelimbs and sternum. Development 120, 2065–2075
    OpenUrlAbstract
Back to top

 Download PDF

Email
JOURNAL ARTICLES
The caudal limit of Otx2 gene expression as a marker of the midbrain/hindbrain boundary: a study using in situ hybridisation and chick/quail homotopic grafts
S. Millet, E. Bloch-Gallego, A. Simeone, R.M. Alvarado-Mallart
Development 1996 122: 3785-3797;
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

An interview with Swathi Arur

Swathi Arur joined the team at Development as an Academic Editor in 2020. Her lab uses multidisciplinary approaches to understand female germline development and fertility. We met with her over Zoom to hear more about her life, her career and her love for C. elegans.

Jim Wells and Hanna Mikkola join our team of Editors

We are pleased to welcome James (Jim) Wells and Hanna Mikkola to our team of Editors. Jim joins us a new Academic Editor, taking over from Gordan Keller, and Hanna joins our team of Associate Editors. Find out more about their research interests and areas of expertise.

New funding scheme supports sustainable events

As part of our Sustainable Conferencing Initiative, we are pleased to announce funding for organisers that seek to reduce the environmental footprint of their event. The next deadline to apply for a Scientific Meeting grant is 26 March 2021.

Read & Publish participation continues to grow

“I’d heard of Read & Publish deals and knew that many universities, including mine, had signed up to them but I had not previously understood the benefits that these deals bring to authors who work at those universities.”

Professor Sally Lowell (University of Edinburgh) shares her experience of publishing Open Access as part of our growing Read & Publish initiative. We now have over 150 institutions in 15 countries and four library consortia taking part – 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. Here, Brandon Carpenter talks about how inherited histone methylation defines the germline versus soma decision in C. elegans. 

Sign up to join our next session:

10 March
Time: TBC
Chaired by: Thomas Lecuit