Summary Mouse Disp 1 is required in sonic hedgehog-expressing cells for paracrine activity of the cholesterol-modified ligand

We have repeated the facial analysis reported in Fig. 2 to provide the data required to support some of the original findings of this study (see Publisher’s note). Our findings substantiate the original conclusions drawn from Fig. 2 of a dose-related genetic interaction between Disp1 and Shh alleles, and of the function of Disp1 within Shh-producing cells. Some differences are reported below, which might reflect slight differences in embryonic staging or increased sensitivity of the whole-mount in situ hybridization procedure here. Importantly, they do not alter the key conclusion that reducing Disp1 levels in Shh-producing cells results in a phenotype similar to that of genetically matched embryos with reduced Disp1 activity throughout the embryo. These data support the overall conclusions of the paper, and, together with other data in the same report, support a model in which the principal requirement for Disp1 activity is in Shh-producing cells.

[1]  C. Tabin,et al.  Mouse Disp1 is required in sonic hedgehog-expressing cells for paracrine activity of the cholesterol-modified ligand , 2004, Development.

[2]  A. McMahon,et al.  Dose dependency of Disp1 and genetic interaction between Disp1 and other hedgehog signaling components in the mouse , 2004, Development.

[3]  A. Schier,et al.  Inactivation of dispatched 1 by the chameleon mutation disrupts Hedgehog signalling in the zebrafish embryo. , 2004, Developmental biology.

[4]  Shan-Mei Xu,et al.  Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates. , 2004, Genes & development.

[5]  L. Ruel,et al.  Cholesterol modification of hedgehog is required for trafficking and movement, revealing an asymmetric cellular response to hedgehog. , 2003, Developmental cell.

[6]  P. Chuang,et al.  Mouse dispatched mutants fail to distribute hedgehog proteins and are defective in hedgehog signaling , 2002, Development.

[7]  A. McMahon,et al.  Efficient gene modulation in mouse epiblast using a Sox2Cre transgenic mouse strain , 2002, Mechanisms of Development.

[8]  A. McMahon,et al.  A direct requirement for Hedgehog signaling for normal specification of all ventral progenitor domains in the presumptive mammalian spinal cord. , 2002, Genes & development.

[9]  J. Taipale,et al.  Hedgehog-Mediated Patterning of the Mammalian Embryo Requires Transporter-like Function of Dispatched , 2002, Cell.

[10]  K. Anderson,et al.  Mouse Dispatched homolog1 Is Required for Long-Range, but Not Juxtacrine, Hh Signaling , 2002, Current Biology.

[11]  A. McMahon,et al.  The whereabouts of a morphogen: direct evidence for short- and graded long-range activity of hedgehog signaling peptides. , 2001, Developmental biology.

[12]  P. Beachy,et al.  Skinny Hedgehog, an Acyltransferase Required for Palmitoylation and Activity of the Hedgehog Signal , 2001, Science.

[13]  Andrew P. McMahon,et al.  Smoothened Mutants Reveal Redundant Roles for Shh and Ihh Signaling Including Regulation of L/R Asymmetry by the Mouse Node , 2001, Cell.

[14]  G. Fishell,et al.  N-terminal fatty-acylation of sonic hedgehog enhances the induction of rodent ventral forebrain neurons. , 2001, Development.

[15]  Xin Zeng,et al.  A freely diffusible form of Sonic hedgehog mediates long-range signalling , 2001, Nature.

[16]  A. McMahon,et al.  Cholesterol Modification of Sonic Hedgehog Is Required for Long-Range Signaling Activity and Effective Modulation of Signaling by Ptc1 , 2001, Cell.

[17]  T. Jessell,et al.  A hedgehog-insensitive form of patched provides evidence for direct long-range morphogen activity of sonic hedgehog in the neural tube. , 2001, Molecular cell.

[18]  G. Fishell,et al.  An acylatable residue of Hedgehog is differentially required in Drosophila and mouse limb development. , 2001, Developmental biology.

[19]  J. Briscoe,et al.  Specification of neuronal fates in the ventral neural tube , 2001, Current Opinion in Neurobiology.

[20]  M. Nakafuku,et al.  Dynamic expression of basic helix-loop-helix Olig family members: implication of Olig2 in neuron and oligodendrocyte differentiation and identification of a new member, Olig3 , 2000, Mechanisms of Development.

[21]  T. Jessell.  Neuronal specification in the spinal cord: inductive signals and transcriptional codes , 2000, Nature Reviews Genetics.

[22]  C. Hui,et al.  Evidence for the differential regulation of Nkx‐6.1 expression in the ventral spinal cord and foregut by Shh‐dependent and ‐independent mechanisms , 2000, Genesis.

[23]  A. McMahon,et al.  Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways. , 2000, Development.

[24]  E. Hafen,et al.  Dispatched, a Novel Sterol-Sensing Domain Protein Dedicated to the Release of Cholesterol-Modified Hedgehog from Signaling Cells , 1999, Cell.

[25]  M. Muenke,et al.  Molecular mechanisms of holoprosencephaly. , 1999, Molecular genetics and metabolism.

[26]  J. Briscoe,et al.  The specification of neuronal identity by graded Sonic Hedgehog signalling. , 1999, Seminars in cell & developmental biology.

[27]  J. Rubenstein,et al.  Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling , 1999, Nature.

[28]  A. Joyner,et al.  Regionalization of Sonic hedgehog transcription along the anteroposterior axis of the mouse central nervous system is regulated by Hnf3-dependent and -independent mechanisms. , 1999, Development.

[29]  R. Paus,et al.  Sonic hedgehog signaling is essential for hair development , 1998, Current Biology.

[30]  A. Joyner,et al.  Gli2 is required for induction of floor plate and adjacent cells, but not most ventral neurons in the mouse central nervous system. , 1998, Development.

[31]  J. Rossant,et al.  Diminished Sonic hedgehog signaling and lack of floor plate differentiation in Gli2 mutant mice. , 1998, Development.

[32]  C. Ambrose,et al.  Identification of a Palmitic Acid-modified Form of Human Sonic hedgehog* , 1998, The Journal of Biological Chemistry.

[33]  T. Jessell,et al.  Pax6 Controls Progenitor Cell Identity and Neuronal Fate in Response to Graded Shh Signaling , 1997, Cell.

[34]  K. G. Coleman,et al.  Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis. , 1997, Science.

[35]  Johan Ericson,et al.  Two Critical Periods of Sonic Hedgehog Signaling Required for the Specification of Motor Neuron Identity , 1996, Cell.

[36]  G. Struhl,et al.  Dual Roles for Patched in Sequestering and Transducing Hedgehog , 1996, Cell.

[37]  P. Beachy,et al.  Cholesterol Modification of Hedgehog Signaling Proteins in Animal Development , 1996, Science.

[38]  P. Beachy,et al.  Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function , 1996, Nature.

[39]  Eugene V Koonin,et al.  Hedgehog Patterning Activity: Role of a Lipophilic Modification Mediated by the Carboxy-Terminal Autoprocessing Domain , 1996, Cell.

[40]  T. Jessell,et al.  Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis , 1995, Cell.

[41]  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.

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

[43]  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.

[44]  N. Schaeren-Wiemers,et al.  A single protocol to detect transcripts of various types and expression levels in neural tissue and cultured cells: in situ hybridization using digoxigenin-labelled cRNA probes , 1993, Histochemistry.

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

[46]  A. McMahon,et al.  Retraction: Dose dependency of Disp1 and genetic interaction between Disp1 and other hedgehog signaling components in the mouse. , 2005, Development.

[47]  Andrew P McMahon,et al.  Developmental roles and clinical significance of hedgehog signaling. , 2003, Current topics in developmental biology.

[48]  Philippe Soriano.  Generalized lacZ expression with the ROSA26 Cre reporter strain , 1999, Nature Genetics.

[49]  T. Jessell,et al.  Graded sonic hedgehog signaling and the specification of cell fate in the ventral neural tube. , 1997, Cold Spring Harbor symposia on quantitative biology.

[50]  D. Wilkinson.  Wholemount in situ hybridization of vertebrate embryos , 1992 .