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JOURNAL ARTICLES
Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development
Y. Furuta, D.W. Piston, B.L. Hogan
Development 1997 124: 2203-2212;

Summary

Bone Morphogenetic Proteins (BMPs) play crucial roles in a variety of developmental processes, but their functions during early vertebrate brain development are largely unknown. To investigate this problem, we have compared by in situ hybridization the expression of five Bmp genes belonging to the Drosophila Decapentaplegic (Bmp2 and Bmp4) and 60A subgroups (Bmp5, Bmp6 and Bmp7). Striking co-expression of these Bmps is observed within the dorsomedial telencephalon, coincident with a future site of choroid plexus development. Bmp co-expression overlaps that of Msx1 and Hfh4, and is complementary to that of Bf1. The domain of Bmp co-expression is also associated with limited growth of the neuroectoderm, as revealed by morphological observation, reduced cell proliferation, and increased local programmed cell death. In vitro experiments using explants from the embryonic lateral telencephalic neuroectoderm reveal that exogenous BMP proteins (BMP4 and BMP2) induce expression of Msx1 and inhibit Bf1 expression, a finding consistent with their specific expression patterns in vivo. Moreover, BMP proteins locally inhibit cell proliferation and increase apoptosis in the explants. These results provide evidence that BMPs function during regional morphogenesis of the dorsal telencephalon by regulating specific gene expression, cell proliferation and local cell death.

REFERENCES

    1. Barlow A. J.,
    2. Francis-West P. H.
    (1997) Ectopic application of recombinant BMP2 and BMP4 can change patterning of developing chick facial primordia. Development 124, 391–398
    OpenUrlAbstract
    1. Brunelli S.,
    2. Faiella A.,
    3. Capra V.,
    4. Nigro V.,
    5. Simeone A.,
    6. Cama A.,
    7. Boncinelli E.
    (1996) Germline mutations in the homeobox gene EMX2 in patients with severe schizencephaly. Nature Genet 12, 94–99
    OpenUrlCrossRefPubMedWeb of Science
    1. Chiang C.,
    2. Litingtung Y.,
    3. Lee E.,
    4. Young K. E.,
    5. Corden J. L.,
    6. Westphal H.,
    7. Beachy P. A.
    (1996) Cyclopia and defective axial patterning in mice lacking Sonic Hedgehog gene function. Nature 383, 407–413
    OpenUrlCrossRefPubMedWeb of Science
    1. Davidson D.
    (1995) The function and evolution of Msx genes: pointers and paradoxes. Trends Genet 11, 405–411
    OpenUrlCrossRefPubMedWeb of Science
    1. Dewulf N.,
    2. Verscheren K.,
    3. Lonnoy O.,
    4. Moren A.,
    5. Grimsby S.,
    6. Spiegle K. V.,
    7. Miyazono K.,
    8. Huylebroeck D.,
    9. Dijke P. T.
    (1995) Distinct spatial and temporal expression patterns of two type I Receptors for bone morphogenetic proteins during mouse embryogenesis. Endocrinology 136, 2652–2663
    OpenUrlCrossRefPubMedWeb of Science
    1. Dudley A. T.,
    2. Lyons K. M.,
    3. Robertson E. J.
    (1995) A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev 9, 2795–2807
    OpenUrlAbstract/FREE Full Text
    1. Ericson J.,
    2. Muhr J.,
    3. Placzek M.,
    4. Lints T.,
    5. Jessel T. M.,
    6. Edlund T.
    (1995) Sonic hedgehog induces the differentiation of ventral forebrain neurons: a common signal for ventral patterning within the neural tube. Cell 81, 747–756
    OpenUrlCrossRefPubMedWeb of Science
    1. Ganan Y.,
    2. Macias D.,
    3. Dterque-Coquillaud M.,
    4. Ros M. A.,
    5. Hurle J. M.
    (1996) Role of TGFand BMPs as signals controlling the position of the digits and the areas of interdigital cell death in the chick limb autopod. Development 122, 2349–2357
    OpenUrlAbstract
    1. Gavrieli Y.,
    2. Sherman Y.,
    3. Ben-Sasson S. A.
    (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J. Cell Biol 119, 493–501
    OpenUrlAbstract/FREE Full Text
    1. Graham A.,
    2. Francis-West P.,
    3. Brikell P.,
    4. Lumsden A.
    (1994) The signalling molecule BMP4 mediates apoptosis in the rhombencephalic neural crest. Nature 372, 684–686
    OpenUrlCrossRefPubMed
    1. Gross R. E.,
    2. Mehler M. F.,
    3. Mabie P. C.,
    4. Zang Z.,
    5. Santschi L.,
    6. Kessler J. A.
    (1996) Bone Morphogenetic Proteins promote astroglyal lineage commitment by mammalian subventricular zone progenitor cells. Neuron 17, 595–606
    OpenUrlCrossRefPubMedWeb of Science
    1. Hill R. E.,
    2. Jones P. F.,
    3. Rees A. R.,
    4. Sime C. M.,
    5. Justice M. J.,
    6. Copeland N. G.,
    7. Jenkins N. A.,
    8. Graham E.,
    9. Davidson D. R.
    (1989). A new family of mouse homeobox-containing genes: molecular structure, chromosomal location, and developmental expression of Hox-7.1. Genes Dev 3, 26–37
    OpenUrlAbstract/FREE Full Text
    1. Hogan B. L. M.
    (1996) Bone morphogenetic proteins: multifunctional regulators of embryonic development. Genes Dev 10, 1580–1594
    OpenUrlFREE Full Text
    1. Jones C. M.,
    2. Lyons K. M.,
    3. Hogan B. L. M.
    (1991) Involvement of bone morphogenetic protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse. Development 111, 531–542
    OpenUrlAbstract
    1. Joyner A. L.
    (1996) Engrailed, Wnt and Pax genes regulate midbrain-hindbrain development. Trends Genet 12, 15–20
    OpenUrlCrossRefPubMedWeb of Science
    1. Kingsley D. M.
    (1994) The TGF-superfamily: new members, new receptors, and new genetic tests of function in different organisms. Genes Dev 8, 133–146
    OpenUrlFREE Full Text
    1. Liem J. K. F.,
    2. Tremml G.,
    3. Roelink H.,
    4. Jessel T. M.
    (1995) Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm. Cell 82, 969–979
    OpenUrlCrossRefPubMedWeb of Science
    1. Lumsden A.,
    2. Krumlauf R.
    (1996) Patterning the vertebrate neuraxis. Science 274, 1109–1115
    OpenUrlAbstract/FREE Full Text
    1. Luo G.,
    2. Hofmann C.,
    3. Bronckers A. L. J. J.,
    4. Sohocki M.,
    5. Bradley A.,
    6. Karsenty G.
    (1995) BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev 9, 2808–2820
    OpenUrlAbstract/FREE Full Text
    1. Lyons K. M.,
    2. Pelton R. W.,
    3. Hogan B. L. M.
    (1989) Patterns of expression of murine Vgr-1 and BMP-2a suggest that TGFβ-like genes coordinately regulate aspects of embryonic development. Genes Dev 3, 1657–1668
    OpenUrlAbstract/FREE Full Text
    1. Lyons K. M.,
    2. Hogan B. L. M.,
    3. Robertson E. J.
    (1995) Colocalization of BMP7 and BMP2 RNAs suggest that these factors cooperatively mediate tissue interactions during murine development. Mech. Dev 50, 71–83
    OpenUrlCrossRefPubMedWeb of Science
    1. Macdonald R.,
    2. Barth K. A.,
    3. Xu Q.,
    4. Holder N.,
    5. Mikkola I.,
    6. Wilson S. W.
    (1995) Midline signal is required for Pax gene regulation and patterning of the eyes. Development 121, 3267–3278
    OpenUrlAbstract
    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. Osumi-Yamashita N.,
    2. Ninomiya Y.,
    3. Doi H.,
    4. Eto K.
    (1994) The contribution of both forebrain and midbrain crest cells to the mesenchyme in the frontonasal mass of mouse embryos. Dev. Biol 164, 409–419
    OpenUrlCrossRefPubMedWeb of Science
    1. Pellegrini M.,
    2. Mansouri A.,
    3. Simeone A.,
    4. Boncinelli E.,
    5. Gruss P.
    (1996) Dentate gyrus formation requires Emx2. Development 122, 3893–3898
    OpenUrlAbstract
    1. Qiu M.,
    2. Anderson S.,
    3. Chen S.,
    4. Meneses J. J.,
    5. Hevner R.,
    6. Kuwana E.,
    7. Pedersen R. A.,
    8. Rubenstein J. L. R.
    (1996) Mutation of the Emx-1 homeobox gene disrupts the corpus callosum. Dev. Biol 178, 174–178
    OpenUrlCrossRefPubMedWeb of Science
    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. Shimeld S. M.,
    2. McKay I. J.,
    3. Sharpe P. T.
    (1996) The murine homeobox gene Msx-3 shows highly restricted expression in the developing neural tube. Mech. Dev 55, 201–210
    OpenUrlCrossRefPubMedWeb of Science
    1. Tao W.,
    2. Lai E.
    (1992) Telencephalon-restricted expression of BF-1, a new member of the HNF-3/fork head gene family in the developing rat brain. Neuron 8, 957–966
    OpenUrlCrossRefPubMedWeb of Science
    1. Thomas T.,
    2. Dziadek M.
    (1993) Capacity to form choroid plexus-like cells in vitro is restricted to specific regions of the mouse neural ectoderm. Development 117, 253–262
    OpenUrlAbstract/FREE Full Text
    1. Vainio S.,
    2. Karavanova I.,
    3. Jowett A.,
    4. Thesleff I.
    (1993) Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development. Cell 75, 45–58
    OpenUrlCrossRefPubMedWeb of Science
    1. Winnier G.,
    2. Blessing M.,
    3. Labosky P. A.,
    4. Hogan B. L. M.
    (1995) Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 9, 2105–2116
    OpenUrlAbstract/FREE Full Text
    1. Xuan S.,
    2. Baptista C. A.,
    3. Balas G.,
    4. Tao W.,
    5. Soares V. C.,
    6. Lai E.
    (1995) Winged helix transcription factor BF-1 is essential for the development of the cerebral hemispheres. Neuron 14, 1141–1152
    OpenUrlCrossRefPubMedWeb of Science
    1. Yoshida M.,
    2. Suda Y.,
    3. Matsuo I.,
    4. Miyamoto N.,
    5. Takeda N.,
    6. Kuratani S.,
    7. Aizawa S.
    (1997) Emx1 and Emx2 functions in development of dorsal telencephalon. Development 124, 101–111
    OpenUrlAbstract
    1. Zhang H.,
    2. Bradley A.
    (1996) Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 122, 2977–2986
    OpenUrlAbstract
    1. Zou H.,
    2. Niswander L.
    (1996) Requirement for BMP signaling in interdigital apoptosis and scale formation. Science 272, 738–741
    OpenUrlAbstract/FREE Full Text
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JOURNAL ARTICLES
Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development
Y. Furuta, D.W. Piston, B.L. Hogan
Development 1997 124: 2203-2212;
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