Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis

The differentiation of floor plate cells and motor neurons can be induced by Sonic hedgehog (SHH), a secreted signaling protein that undergoes autoproteolytic cleavage to generate amino- and carboxy-terminal products. We have found that both floor plate cells and motor neurons are induced by the amino-terminal cleavage product of SHH (SHH-N). The threshold concentration of SHH-N required for motor neuron induction is about 5-fold lower than that required for floor plate induction. Higher concentrations of SHH-N can induce floor plate cells at the expense of motor neuron differentiation. Our results suggest that the induction of floor plate cells and motor neurons by the notochord in vivo is mediated by exposure of neural plate cells to different concentrations of the amino-terminal product of SHH autoproteolytic cleavage.

[1]  M. Seldin,et al.  Products, genetic linkage and limb patterning activity of a murine hedgehog gene. , 1994, Development.

[2]  J. J. Lee,et al.  Autoproteolysis in hedgehog protein biogenesis. , 1994, Science.

[3]  T. Jessell,et al.  Control of cell pattern in the neural tube: Motor neuron induction by diffusible factors from notochord and floor plate , 1993, Cell.

[4]  M. Tessier-Lavigne,et al.  Patterning of mammalian somites by surface ectoderm and notochord: Evidence for sclerotome induction by a hedgehog homolog , 1994, Cell.

[5]  W. N. Burnette,et al.  "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. , 1981, Analytical biochemistry.

[6]  T. Jessell,et al.  Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes , 1994, Cell.

[7]  P. Ingham.  Localized hedgehog activity controls spatial limits of wingless transcription in the Drosophila embryo , 1993, Nature.

[8]  K. Obata,et al.  Developmental changes in unique cell surface antigens of chick embryo spinal motoneurons and ganglion cells. , 1984, Developmental biology.

[9]  T. Jessell,et al.  Early stages of motor neuron differentiation revealed by expression of homeobox gene Islet-1. , 1992, Science.

[10]  T. Jessell,et al.  Mesodermal control of neural cell identity: floor plate induction by the notochord. , 1990, Science.

[11]  T. Jessell,et al.  Restrictions to Floor Plate Induction by hedgehog and Winged-Helix Genes in the Neural Tube of Frog Embryos , 1995, Molecular and Cellular Neuroscience.

[12]  Andrew R. Cherenson,et al.  The structure of an antigenic determinant in a protein , 1984, Cell.

[13]  C. Bordier.  Phase separation of integral membrane proteins in Triton X-114 solution. , 1981, The Journal of biological chemistry.

[14]  J. Darnell,et al.  Hepatocyte nuclear factor 3/fork head or "winged helix" proteins: a family of transcription factors of diverse biologic function. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Andrew P. McMahon,et al.  Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity , 1993, Cell.

[16]  G. Struhl,et al.  Protein kinase A and hedgehog signaling in drosophila limb development , 1995, Cell.

[17]  T. Jessell,et al.  Floor plate-derived signals and the control of neural cell pattern in vertebrates. , 1990, Harvey lectures.

[18]  T. Jessell,et al.  Early stages of notochord and floor plate development in the chick embryo defined by normal and induced expression of HNF-3 beta. , 1995, Developmental biology.

[19]  J. Darnell,et al.  Sequential expression of HNF-3β and HNF-3α by embryonic organizing centers: the dorsal lip/node, notochord and floor plate , 1993, Mechanisms of Development.

[20]  Stephen C. Ekker,et al.  The product of hedgehog autoproteolytic cleavage active in local and long-range signalling , 1995, Nature.

[21]  Gerald M. Rubin,et al.  The TGFβ homolog dpp and the segment polarity gene hedgehog are required for propagation of a morphogenetic wave in the Drosophila retina , 1993, Cell.

[22]  T. Jessell,et al.  Induction of floor plate differentiation by contact-dependent, homeogenetic signals. , 1993, Development.

[23]  R. Ho,et al.  The cyclops mutation blocks specification of the floor plate of the zebrafish central nervous system , 1991, Nature.

[24]  Konrad Basler,et al.  Organizing activity of wingless protein in Drosophila , 1993, Cell.

[25]  C. Nüsslein-Volhard,et al.  Mutations affecting segment number and polarity in Drosophila , 1980, Nature.

[26]  B. Hogan,et al.  HNF-3β as a regulator of floor plate development , 1994, Cell.

[27]  T. Lints,et al.  Sonic hedgehog induces the differentiation of ventral forebrain neurons: A common signal for ventral patterning within the neural tube , 1995, Cell.

[28]  T. Jessell,et al.  Control of cell pattern in the neural tube: Regulation of cell differentiation by dorsalin-1, a novel TGFβ family member , 1993, Cell.

[29]  Mary Ellen Lane,et al.  Function of protein kinase A in hedgehog signal transduction and Drosophila imaginal disc development , 1995, Cell.

[30]  Konrad Basler,et al.  Compartment boundaries and the control of Drosopfiffa limb pattern by hedgehog protein , 1994, Nature.

[31]  I. Guerrero,et al.  Targeted expression of the signaling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings. , 1994, The EMBO journal.

[32]  T. Tabata,et al.  The Drosophila hedgehog gene is expressed specifically in posterior compartment cells and is a target of engrailed regulation. , 1992, Genes & development.

[33]  T. Jessell,et al.  Induction of motor neurons by Sonic hedgehog is independent of floor plate differentiation , 1995, Current Biology.

[34]  J. Smith.  Dorso-ventral patterning in the neural tube , 1993, Current Biology.

[35]  A. Rosenthal,et al.  Neurotrophin 3 stimulates the differentiation of motoneurons from avian neural tube progenitor cells. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[36]  T. Tabata,et al.  Hedgehog is a signaling protein with a key role in patterning Drosophila imaginal discs , 1994, Cell.

[37]  M. Tessier-Lavigne,et al.  Control of neuronal diversity by the floor plate: Contact-mediated induction of midbrain dopaminergic neurons , 1995, Cell.

[38]  P. Beachy,et al.  Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog , 1992, Cell.

[39]  J. Mohler,et al.  Molecular organization and embryonic expression of the hedgehog gene involved in cell-cell communication in segmental patterning of Drosophila. , 1992, Development.

[40]  T. Jessell,et al.  Control of cell pattern in the developing nervous system: Polarizing activity of the floor plate and notochord , 1991, Cell.

[41]  S. Higashijima,et al.  Structure and expression of hedgehog, a Drosophila segment-polarity gene required for cell-cell communication. , 1993, Gene.

[42]  P. Ingham,et al.  A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos , 1993, Cell.

[43]  S. DiNardo,et al.  Drosophila hedgehog acts as a morphogen in cellular patterning , 1994, Cell.

[44]  C. Tabin,et al.  Sonic hedgehog mediates the polarizing activity of the ZPA , 1993, Cell.

[45]  P. Rigby,et al.  High efficiency gene transfer into mammalian cells. , 1984, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[46]  T. Jessell,et al.  Ectopic neural expression of a floor plate marker in frog embryos injected with the midline transcription factor Pintallavis. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[47]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[48]  S. Thor,et al.  The homeodomain LIM protein Isl-1 is expressed in subsets of neurons and endocrine cells in the adult rat , 1991, Neuron.

[49]  R. Krumlauf,et al.  Evidence for a mitogenic effect of Wnt-1 in the developing mammalian central nervous system. , 1994, Development.

[50]  Saigo Kaoru,et al.  Structure and expression of hedgehog, a Drosophila segment-polarity gene required for cell-cell communication. , 1993 .

[51]  G. Rubin,et al.  cAMP-dependent protein kinase and hedgehog act antagonistically in regulating decapentaplegic transcription in drosophila imaginal discs , 1995, Cell.

[52]  A. McMahon,et al.  Proteolytic processing yields two secreted forms of sonic hedgehog , 1995, Molecular and cellular biology.

[53]  K. Moses,et al.  The segment polarity gene hedgehog is required for progression of the morphogenetic furrow in the developing Drosophila eye , 1993, Cell.

[54]  Viktor Hamburger,et al.  A series of normal stages in the development of the chick embryo , 1992, Journal of morphology.

[55]  T. Jessell,et al.  Control of dorsoventral pattern in vertebrate neural development: induction and polarizing properties of the floor plate. , 1991, Development (Cambridge, England). Supplement.

[56]  J. Sanes,et al.  Lineage, arrangement, and death of clonally related motoneurons in chick spinal cord , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[57]  M. Tessier-Lavigne,et al.  Long-range sclerotome induction by sonic hedgehog: Direct role of the amino-terminal cleavage product and modulation by the cyclic AMP signaling pathway , 1995, Cell.

[58]  T. Jessell,et al.  Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord , 1994, Cell.