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JOURNAL ARTICLES
Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites
K.F. Liem, T.M. Jessell, J. Briscoe
Development 2000 127: 4855-4866;

Summary

The secretion of Sonic hedgehog (Shh) from the notochord and floor plate appears to generate a ventral-to-dorsal gradient of Shh activity that directs progenitor cell identity and neuronal fate in the ventral neural tube. In principle, the establishment of this Shh activity gradient could be achieved through the graded distribution of the Shh protein itself, or could depend on additional cell surface or secreted proteins that modify the response of neural cells to Shh. Cells of the neural plate differentiate from a region of the ectoderm that has recently expressed high levels of BMPs, raising the possibility that prospective ventral neural cells are exposed to residual levels of BMP activity. We have examined whether modulation of the level of BMP signaling regulates neural cell responses to Shh, and thus might contribute to the patterning of cell types in the ventral neural tube. Using an in vitro assay of neural cell differentiation we show that BMP signaling markedly alters neural cell responses to Shh signals, eliciting a ventral-to-dorsal switch in progenitor cell identity and neuronal fate. BMP signaling is regulated by secreted inhibitory factors, including noggin and follistatin, both of which are expressed in or adjacent to the neural plate. Conversely, follistatin but not noggin produces a dorsal-to-ventral switch in progenitor cell identity and neuronal fate in response to Shh both in vitro and in vivo. These results suggest that the specification of ventral neural cell types depends on the integration of Shh and BMP signaling activities. The net level of BMP signaling within neural tissue may be regulated by follistatin and perhaps other BMP inhibitors secreted by mesodermal cell types that flank the ventral neural tube.

REFERENCES

    1. Acampora D.,
    2. Gulisano M.,
    3. Simone A.
    (1999) Otx genes and the genetic control of brain morphogenesis. Mol. Cell Neurosci 13, 1–8
    OpenUrlCrossRefPubMed
    1. Amthor H.,
    2. Connolly D.,
    3. Patel. K.,
    4. Brand-Saberi B.,
    5. Wilkinson D.,
    6. Cooke J.,
    7. Christ. B.
    (1996) The Expression and regulation of follistatin and a follistatin-like gene during avian somite compartmentalization and myogenesis. Dev.Biol 178, 343–362
    OpenUrlCrossRefPubMedWeb of Science
    1. Arkell R.,
    2. Beddington R. S. P.
    (1997) BMP7 influences pattern and growth of the developing hindbrain of mouse embryos. Development 124, 1–12
    OpenUrlAbstract
    1. Barth K. A.,
    2. Kishimoto Y.,
    3. Rohr K. B.,
    4. Seydler C.,
    5. Schulte-Merker S.,
    6. Wilson S. W.
    (1999) BMP activity establishes a gradient of positional information throughout the entire neural plate. Development 126, 4977–4987
    OpenUrlAbstract
    1. Basler K.,
    2. Edlund T.,
    3. Jessell T. M.,
    4. Yamada T.
    (1993) Control of cell pattern in the Neural tube: Regulation of cell differentiation by dorsalin-1, a novel TGFfamily member. Cell 73, 687–702
    OpenUrlCrossRefPubMedWeb of Science
    1. Briscoe J.,
    2. Sussel L.,
    3. Serup D.,
    4. Hartigan-O'Connor D.,
    5. Jessell T. M.,
    6. Rubenstein J. L. R.,
    7. Ericson J.
    (1999). Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic Hedgehog signaling. Nature 398, 622–627
    OpenUrlCrossRefPubMed
    1. Briscoe J.,
    2. Pierani A.,
    3. Jessell T. M.,
    4. Ericson J.
    (2000) A homeodomainprotein code specifies progenitor cell identity and neuronal fate in the ventral neural tube. Cell 101, 435–445
    OpenUrlCrossRefPubMedWeb of Science
    1. Bruneau S.,
    2. Rosa F. M.
    (1997) Dynamo, a new zebrafish DVR member of the TGFsuperfamily is expressed in the posterior neural tube and is up-regulated by Sonic Hedgehog. Mech. Dev 61, 199–212
    OpenUrlCrossRefPubMedWeb of Science
    1. Capdevila J.,
    2. Johnson R. L.
    (1998) Endogenous and ectopic expression of noggin suggests a conserved mechanism for regulation of BMP function during limb and somite patterning. Dev. Biol 197, 205–217
    OpenUrlCrossRefPubMedWeb of Science
    1. Chuang P.-T.,
    2. McMahon A. P.
    (1999) Vertebrate hedgehog signaling modulated by induction of a Hedgehog-binding protein. Nature 397, 617–621
    OpenUrlCrossRefPubMedWeb of Science
    1. Connolly D. J.,
    2. Patel K.,
    3. Cooke J.
    (1997) Chick noggin is expressed in the organizer and neural plate during axial development, but offers no evidence of involvement in primary axis formation. Int. J. Dev. Biol 41, 389–396
    OpenUrlPubMedWeb of Science
    1. Dale J. K.,
    2. Vesque C.,
    3. Lints T.,
    4. Sampath T. K.,
    5. Furley A.,
    6. Dodd J.,
    7. Placzek M.
    (1997) Cooperation of BMP7 and Shh in the induction of forebrain ventral midline cells by prechordal mesoderm. Cell 90, 257–269
    OpenUrlCrossRefPubMedWeb of Science
    1. Dale K.,
    2. Sattar N.,
    3. Heemskerk J.,
    4. Clarke J. D.,
    5. Placzek M.,
    6. Dodd J.
    (1999) Differential patterning of ventral midline cells by axial mesoderm is regulated by BMP7 and chordin. Development 26, 397–408
    OpenUrl
    1. Epstein D. J.,
    2. Marti E.,
    3. Scott M. P.,
    4. McMahon A. P.
    (1996) Antagonizing camp-dependent protein kinase A in the dorsal CNS activates a conserved Sonic hedgehog signaling pathway. Development 122, 2885–2894
    OpenUrlAbstract
    1. Ericson J.,
    2. Thor S.,
    3. Edlund T.,
    4. Jessell T. M.,
    5. Yamada T.
    (1992) Early stages of motor neuron differentiation revealed by expression of homeobox gene Islet-1. Science 256, 1555–1560
    OpenUrlAbstract/FREE Full Text
    1. Ericson J.,
    2. Morton S.,
    3. Kawakami A.,
    4. Roelink H.,
    5. Jessell T. M.
    (1996) Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity. Cell 87, 661–673
    OpenUrlCrossRefPubMedWeb of Science
    1. Ericson J.,
    2. Rashbass P.,
    3. Schedl A.,
    4. Brenner-Morton S.,
    5. Kawakami A.,
    6. van Heyningen V.,
    7. Jessell T. M.,
    8. Briscoe J.
    (1997) Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling. Cell 90, 169–180
    OpenUrlCrossRefPubMedWeb of Science
    1. Ericson J.,
    2. Briscoe J.,
    3. Rashbass P.,
    4. van Heyningen V.,
    5. Jessell T. M.
    (1997) Graded Sonic Hedgehog signaling and the specification of cell fate in the ventral neural tube. Cold Spring Harb. Symp. Quant. Biol 62, 451–466
    OpenUrlAbstract/FREE Full Text
    1. Fainsod A.,
    2. Steinbeisser H.,
    3. De Robertis E. M.
    (1994) On the function of BMP-4 in patterning the marginal zone of the Xenopus embryo. EMBO J 13, 5015–5025
    OpenUrlPubMedWeb of Science
    1. Fan C. M.,
    2. Porter J. A.,
    3. Chiang C.,
    4. Chang D. T.,
    5. Beachy P. A.,
    6. Tessier-Lavigne M.
    (1995) Long-range sclerotome induction by sonic hedgehog: direct role of the amino-terminal cleavage product and modulation by the cyclic AMP signaling pathway. Cell 81, 457–465
    OpenUrlCrossRefPubMedWeb of Science
    1. Fuse N.,
    2. Maiti T.,
    3. Wang B.,
    4. Porter J. A.,
    5. Hall T. M.,
    6. Leahy D. J.,
    7. Beachy P. A.
    (1999) Sonic hedgehog protein signals not as a hydrolytic enzyme but as an apparent ligand for patched. Proc. Natl. Acad. Sci. USA 96, 10992–10999
    OpenUrlAbstract/FREE Full Text
    1. Goodrich L. V.,
    2. Johnson R. L.,
    3. Milenkovic L.,
    4. McMahon J. A.,
    5. Scott M. P.
    (1996) Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog. Genes Dev 10, 301–312
    OpenUrlAbstract/FREE Full Text
    1. Graham A.,
    2. Lumsden A.
    (1996) Interaction between rhombomeres modulate krox-20 and follistatin expression in the chick embryo hindbrain. Development 122, 473–480
    OpenUrlAbstract
    1. Hamburger V.,
    2. Hamilton H. L.
    (1951) A series of normal stages in the development of chick embryos. J. Morph 88, 49–92
    OpenUrlCrossRefPubMedWeb of Science
    1. Hammerschmidt M.,
    2. Brook A.,
    3. McMahon A. P.
    (1997) The world according to hedgehog. Trends Genet 13, 14–21
    OpenUrlCrossRefPubMedWeb of Science
    1. Hynes M.,
    2. Porter J. A.,
    3. Chiang C.,
    4. Chang D.,
    5. Tessier-Lavigne M.,
    6. Beachy P. A.,
    7. Rosenthal A.
    (1995) Induction of midbrain dopaminergic neurons by Sonic hedgehog. Neuron 15, 35–44
    OpenUrlCrossRefPubMedWeb of Science
    1. Iemura S.,
    2. Yammamoto T. S.,
    3. Takagi C.,
    4. Uchiyama H.,
    5. Natsume T.,
    6. Shimasaki S.,
    7. Sugino H.,
    8. Ueno N.
    (1998) Direct binding of follistatin to a complex of bone-morphogenetic protein and its receptor inhibits ventral and epidermal cell fates in early Xenopus embryo. Proc. Natl. Acad. Sci. USA 95, 9337–9342
    OpenUrlAbstract/FREE Full Text
    1. Ingham P. W.
    (1998) Transducing hedgehog: the story so far. EMBO J 17, 3505–3511
    OpenUrlAbstract
    1. Jones C. M.,
    2. Lyons K. M.,
    3. Hogan B. L.
    (1991) Involvement of BoneMorphogenetic Protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse. Development 111, 531–542
    OpenUrlAbstract
    1. Lee K. J.,
    2. Mendelsohn M.,
    3. Jessell T. M.
    (1998) Neuronal patterning by BMPs: a requirement for GDF7 in the generation of a discrete class of commissural interneurons in the mouse spinal cord. Genes Dev 12, 3394–3407
    OpenUrlAbstract/FREE Full Text
    1. Lee K. J.,
    2. Jessell T. M.
    (1999) The specification of dorsal cell fates in the vertebrate central nervous system. Annu. Rev. Neurosci 22, 261–294
    OpenUrlCrossRefPubMedWeb of Science
    1. Lee K. J.,
    2. Dietrich P.,
    3. Jessell T. M.
    (2000) Genetic abalation reveals that the roof plate is essential for dorsal interneuron specification. Nature 403, 734–740
    OpenUrlCrossRefPubMed
    1. Liem K. F., Jr.,
    2. Tremml G.,
    3. Roelink H.,
    4. Jessell 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. Liem K. F., Jr.,
    2. Tremml G.,
    3. Jessell T. M.
    (1997) A role for the roof plate and its resident TGF-related proteins in neuronal patterning in the dorsal spinal cord. Cell 91, 127–138
    OpenUrlCrossRefPubMedWeb of Science
    1. Liu F.,
    2. Massague J.,
    3. Ruiz i Altaba A.
    (1998) Carboxy-terminally truncated gli3 proteins associate with smads. Nat. Genet 20, 325–326
    OpenUrlCrossRefPubMedWeb of Science
    1. Lumsden A.,
    2. Krumlauf R.
    (1996) Pattering the vertebrate neuraxis. Science 274, 1109–1115
    OpenUrlAbstract/FREE Full Text
    1. Marigo V.,
    2. Scott M. P.,
    3. Johnson R. L.,
    4. Goodrich L. V.,
    5. Tabin C. J.
    (1996) Conservation in hedgehog signaling: induction of a chicken patched homologue by Sonic Hedgehog in the developing limb. Development 122, 1225–1233
    OpenUrlAbstract
    1. Marigo V.,
    2. Tabin C. J.
    (1996) Regulation of patched by Sonic hedgehog in the developing neural tube. Proc. Nat. Acad. Sci. USA 93, 9346–9351
    OpenUrlAbstract/FREE Full Text
    1. Marti E.,
    2. Bumcrot D. A.,
    3. Takada R.,
    4. McMahon A. P.
    (1995) Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants. Nature 375, 322–325
    OpenUrlCrossRefPubMed
    1. Martinez-Morales J. R.,
    2. Barbas J. A.,
    3. Marti E.,
    4. Bovalenta P.,
    5. Edgar D.,
    6. Rodriguez-Tebar A.
    (1997) Vitronectin is expressed in the ventral region of the neural tube and promotes the differentiation of motor neurons. Development 124, 139–147
    OpenUrl
    1. Matzuk M. M.,
    2. Lu N.,
    3. Vogel H.,
    4. Sellheyer K.,
    5. Roop D. R.,
    6. Bradley A.
    (1995) Multiple defects and perinatal death in mice deficient in follistatin. Nature 374, 360–363
    OpenUrlCrossRefPubMed
    1. McMahon J. A.,
    2. Takada S.,
    3. Zimmerman L. B.,
    4. Fan C. M.,
    5. Harland R. M.,
    6. McMahon A. P.
    (1998) Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev 12, 1438–52
    OpenUrlAbstract/FREE Full Text
    1. Mullen R. J.,
    2. Buck C. R.,
    3. Smith A. M.
    (1992) NeuN, a neuronal specific nuclear protein in vertebrates. Development 116, 201–211
    OpenUrlAbstract
    1. Murone M.,
    2. Rosenthal A.,
    3. de Sauvage F. J.
    (1999) Hedgehog signal transduction: from flies to vertebrates. Exp. Cell Res 253, 25–33
    OpenUrlCrossRefPubMedWeb of Science
    1. Nakamura T.,
    2. Takio K.,
    3. Eto Y.,
    4. Shibai H.,
    5. Titani K.,
    6. Sugino H.
    (1990) Activin-binding protein from rat ovary is follistatin. Science 247, 836–838
    OpenUrlAbstract/FREE Full Text
    1. Nothias F.,
    2. Fishell G.,
    3. Ruiz i Altaba A.
    (1998) Cooperation of intrinsic and extrinsic signals in the elaboration of regional identity in the posterior cerebral cortex. Curr. Biol 8, 459–462
    OpenUrlCrossRefPubMedWeb of Science
    1. Nguyen V. H.,
    2. Trout J.,
    3. Connors S. A.,
    4. Andermann P.,
    5. Weinberg E.,
    6. Mullins M. C.
    (2000) Dorsal and intermediate neuronal cell types of the spinal cord are established by a BMP signaling pathway. Development 127, 1209–1220
    OpenUrlAbstract
    1. Patel K.,
    2. Connolly D. J.,
    3. Amthor H.,
    4. Nose K.,
    5. Cooke J.
    (1996) Cloning and early dorsal axial expression of Flik, and chick Follistatin-related gene: evidence for involvement in dorsalization/neural induction. Dev. Biol 178, 327–342
    OpenUrlCrossRefPubMedWeb of Science
    1. Pepinsky R. B.,
    2. Rayhorn P.,
    3. Day E. S.,
    4. Dergay A.,
    5. Williams K. P.,
    6. Galdes A.,
    7. Taylor F. R.,
    8. Boriack-Sjodin P. A.,
    9. Garber E. A.
    (2000) Mapping sonic hedgehog-receptor interactions by steric interference. J. Biol. Chem 275, 10995–11001
    OpenUrlAbstract/FREE Full Text
    1. Piccolo S.,
    2. Sasai Y.,
    3. Lu B.,
    4. De Robertis E. M.
    (1996) Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct binding of chordin to BMP-4. Cell 86, 589–598
    OpenUrlCrossRefPubMedWeb of Science
    1. Pierani A.,
    2. Brenner-Morton S.,
    3. Chiang C.,
    4. Jessell T. M.
    (1999) A Sonic Hedgehog-independent, retinoid-activated pathway of neurogenesis in the ventral spinal cord. Cell 97, 1–20
    OpenUrlCrossRefPubMedWeb of Science
    1. Pons S.,
    2. Marti E.
    (2000) Sonic Hedgehog synergizes with the extracellular matrix protein Vitronectin to induce spinal motor neuron differentiation. Development 127, 333–342
    OpenUrlAbstract
    1. Porter J. A.,
    2. von Kessler D. P.,
    3. Ekker S. C.,
    4. Young K. E.,
    5. Lee J. J.,
    6. Moses K.,
    7. Beachy P. A.
    (1995) The product of hedgehog autoproteolytic cleavage active in local and long-range signaling. Nature 374, 363–366
    OpenUrlCrossRefPubMedWeb of Science
    1. Quirk J.,
    2. van den Heuvel M.,
    3. Henrique D.,
    4. Marigo V.,
    5. Jones T. A.,
    6. Tabin C.,
    7. Ingham P. W.
    (1997) The smoothened gene and hedgehog signal transduction in Drosophila and vertebrate development. Cold Spring Harb. Symp. Quant. Biol 62, 217–226
    OpenUrlAbstract/FREE Full Text
    1. Roelink H.,
    2. Porter J. A.,
    3. Chiang C.,
    4. Tanabe Y.,
    5. Chang D. T.,
    6. Beachy P. A.,
    7. Jessell T. M.
    (1995) Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis. Cell 81, 445–455
    OpenUrlCrossRefPubMedWeb of Science
    1. Ruiz i Altaba A.,
    2. Placzek M.,
    3. Baldassare M.,
    4. Dodd J.,
    5. Jessell T. M.
    (1995) Early stages of notochord and floor plate development in the chick embryo defined by normal and induced expression of HNF3. Dev. Biol 170, 299–313
    OpenUrlCrossRefPubMedWeb of Science
    1. Sasaki H.,
    2. Hui C.,
    3. Nakafuku M.,
    4. Kondoh H.
    (1997) A binding site for gli proteins is essential for HNF3floor plate enhancer activity in transgenics and can respond to Shh in vitro. Development 124, 1313–1322
    OpenUrlAbstract
    1. Smith W. C.
    (2000) TGF beta inhibitors. New and unexpected requirements in vertebrate development. Trends Genet 15, 3–5
    OpenUrl
    1. Stone D. M.,
    2. Hynes M.,
    3. Armanini M.,
    4. Swanson T. A.,
    5. Gu Q.,
    6. Johnson R. L.,
    7. Scott M. P.,
    8. Pennica D.,
    9. Goddard A.,
    10. Phillips H.,
    11. Noll M.,
    12. Hooper J. E.,
    13. de Sauvage F.,
    14. Rosenthal A.
    (1996) The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature 384, 129–134
    OpenUrlCrossRefPubMedWeb of Science
    1. Streit A.,
    2. Lee K. J.,
    3. Woo I.,
    4. Roberts C.,
    5. Jessell T. M.,
    6. Stern C.
    (1998) Chordin regulates primitive streak development and the stability of induced neural cells, but is not sufficient for neural induction in the chick embryo. Development 125, 507–519
    OpenUrlAbstract
    1. Streit A.,
    2. Stern C. D.
    (1999) Establishment and maintenance of the border of the neural plate in the chick: involvement of FGF and BMP activity. Mech Dev 82, 51–66
    OpenUrlCrossRefPubMedWeb of Science
    1. Sussel L.,
    2. Marin O.,
    3. Kimura S.,
    4. Rubenstein J. L.
    (1999). Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum. Development 126, 3359–3370
    OpenUrlAbstract
    1. Tanabe Y.,
    2. Jessell T. M.
    (1996) Diversity and pattern in the developing spinal cord. Science 274, 1115–1123
    OpenUrlAbstract/FREE Full Text
    1. Tanabe Y.,
    2. Roelink H.,
    3. Jessell T. M.
    (1995) Induction of motor neurons by Sonic hedgehog is independent of floor plate differentiation. Curr. Biol 5, 651–658
    OpenUrlCrossRefPubMedWeb of Science
    1. Thery C.,
    2. Sharpe M. J.,
    3. Batley S. J.,
    4. Stern C. D.,
    5. Gherardi E.
    (1995) Expression of HGF/SF, HGF1/MSP, and c-met suggests new functions during early chick development. Dev. Genet 17, 90–101
    OpenUrlCrossRefPubMedWeb of Science
    1. Towers P.,
    2. Patel K.,
    3. Withington S.,
    4. Isaac A.,
    5. Cooke J.
    (1999) Flik, a chick follistatin-related gene, functions in gastrula dorsalisation/neural induction and in subsequent maintenance of midline sonic hedgehog signaling. Dev. Biol 214, 298–317
    OpenUrlCrossRefPubMedWeb of Science
    1. Tsuchida T.,
    2. Ensini M.,
    3. Morton S.,
    4. Baldassare M.,
    5. Edlund T.,
    6. Jessell T. M.,
    7. Pfaff S.
    (1994) Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes. Cell 79, 957–970
    OpenUrlCrossRefPubMedWeb of Science
    1. Varela-Echavarria A.,
    2. Pfaff S. L.,
    3. Guthrie S.
    (1996) Differential expression of LIM homeobox genes among motor neuron subpopulations in the developing chick brain stem. Mol. Cell Neurosci 8, 242–257
    OpenUrlCrossRefPubMedWeb of Science
    1. Waschek J. A.,
    2. Castillas R. A.,
    3. Nguyen T. T.,
    4. DiCicco-Bloom E. M.,
    5. Carpenter E. M.,
    6. Rodriguez W. I.
    (1998) Neural tube expression of pituitary adenylate cyclase-activating peptide (PACAP) and receptor: potential role in patterning and neurogenesis. Proc. Natl. Acad. Sci. USA 95, 9602–9607
    OpenUrlAbstract/FREE Full Text
    1. Whitman M.
    (1998) Smads and early developmental signaling by the TGFsuperfamily. Genes Dev 12, 2445–2462
    OpenUrlFREE Full Text
    1. Yamada T.,
    2. Placzek M.,
    3. Tanaka H.,
    4. Dodd J.,
    5. Jessell T. M.
    (1991) Control of cell pattern in the developing nervous system: polarizing activity of the floor plate and notochord. Cell 64, 635–647
    OpenUrlCrossRefPubMedWeb of Science
    1. Yamada T.,
    2. Pfaff S. L.,
    3. Edlund T.,
    4. Jessell T. M.
    (1993) Control of cell pattern in the neural tube: Motor neuron induction by diffusible factors from notochord and floor plate. Cell 73, 673–686
    OpenUrlCrossRefPubMedWeb of Science
    1. Yamashita H.,
    2. ten Dijke P.,
    3. Huylebroeck D.,
    4. Sampath T. K.,
    5. andries M.,
    6. Smith J. C.,
    7. Heldin C.,
    8. Miyazono K.
    (1995) Osteogenic protein-1 binds to activin type II receptors and induces certain Activin-like effects. J. Cell Biol 130, 217–226
    OpenUrlAbstract/FREE Full Text
    1. Zimmerman L.,
    2. De Jesus-Escobar J.,
    3. Harland R.
    (1996) The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein-4. Cell 86, 599–606
    OpenUrlCrossRefPubMedWeb of Science
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JOURNAL ARTICLES
Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites
K.F. Liem, T.M. Jessell, J. Briscoe
Development 2000 127: 4855-4866;
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