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Genes Dev
2002 Nov 15;1622:2849-64. doi: 10.1101/gad.1025702.
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A direct requirement for Hedgehog signaling for normal specification of all ventral progenitor domains in the presumptive mammalian spinal cord.
Wijgerde M
,
McMahon JA
,
Rule M
,
McMahon AP
.
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The hedgehog signaling pathway organizes the developing ventral neural tube by establishing distinct neural progenitor fates along the dorsoventral axis. Smoothened (Smo) is essential for all Hedgehog (Hh) signaling, and genetic inactivation of Smo cells autonomously blocks the ability of cells to transduce the Hh signal. Using a chimeric approach, we examined the behavior of Smo null mutant neural progenitor cells in the developing vertebrate spinal cord, and we show that direct Hh signaling is essential for the specification of all ventral progenitor populations. Further, Hh signaling extends into the dorsal half of the spinal cord including the intermediate Dbx expression domain. Surprisingly, in the absence of Sonic hedgehog (Shh), we observe the presence of a Smo-dependent Hh signaling activity operating in the ventral half of the spinal cord that most likely reflects Indian hedgehog (Ihh) signaling originating from the underlying gutendoderm. Comparative studies of Shh, Smo, and Gli3 single and compound mutants reveal that Hh signaling acts in part to specify neural cell identity by counteracting the repressive action of Gli3 on p0, p1, p2, and pMN formation. However, whereas these cell identities are restored in Gli3/Smo compound mutants, correct stratification of the rescued ventral cell types is lost. Thus, Hh signaling is essential for organizing ventral cell pattern, possibly through the control of differential cell affinities.
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12435628
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Aza-Blanc,
Proteolysis that is inhibited by hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a repressor.
1997, Pubmed
Aza-Blanc,
Proteolysis that is inhibited by hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a repressor.
1997,
Pubmed
Blair,
Smoothened-mediated Hedgehog signalling is required for the maintenance of the anterior-posterior lineage restriction in the developing wing of Drosophila.
1997,
Pubmed
Briscoe,
A hedgehog-insensitive form of patched provides evidence for direct long-range morphogen activity of sonic hedgehog in the neural tube.
2001,
Pubmed
Briscoe,
A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube.
2000,
Pubmed
Briscoe,
Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling.
1999,
Pubmed
Briscoe,
Specification of neuronal fates in the ventral neural tube.
2001,
Pubmed
Bumcrot,
Proteolytic processing yields two secreted forms of sonic hedgehog.
1995,
Pubmed
,
Xenbase
Burrill,
PAX2 is expressed in multiple spinal cord interneurons, including a population of EN1+ interneurons that require PAX6 for their development.
1997,
Pubmed
Chamoun,
Skinny hedgehog, an acyltransferase required for palmitoylation and activity of the hedgehog signal.
2001,
Pubmed
Denef,
Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened.
2000,
Pubmed
Ding,
Diminished Sonic hedgehog signaling and lack of floor plate differentiation in Gli2 mutant mice.
1998,
Pubmed
,
Xenbase
Echelard,
Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity.
1993,
Pubmed
Eggenschwiler,
Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway.
2001,
Pubmed
Ericson,
Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling.
1997,
Pubmed
,
Xenbase
Ericson,
Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity.
1996,
Pubmed
Friedrich,
Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice.
1991,
Pubmed
Fu,
Dual origin of spinal oligodendrocyte progenitors and evidence for the cooperative role of Olig2 and Nkx2.2 in the control of oligodendrocyte differentiation.
2002,
Pubmed
Goodrich,
Overexpression of ptc1 inhibits induction of Shh target genes and prevents normal patterning in the neural tube.
1999,
Pubmed
Goodrich,
Altered neural cell fates and medulloblastoma in mouse patched mutants.
1997,
Pubmed
Goodrich,
Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog.
1996,
Pubmed
Gritli-Linde,
The whereabouts of a morphogen: direct evidence for short- and graded long-range activity of hedgehog signaling peptides.
2001,
Pubmed
Hahn,
The patched signaling pathway in tumorigenesis and development: lessons from animal models.
1999,
Pubmed
Hatini,
Divide and conquer: pattern formation in Drosophila embryonic epidermis.
2001,
Pubmed
Helms,
Progenitors of dorsal commissural interneurons are defined by MATH1 expression.
1998,
Pubmed
Incardona,
Receptor-mediated endocytosis of soluble and membrane-tethered Sonic hedgehog by Patched-1.
2000,
Pubmed
Ingham,
Hedgehog signaling in animal development: paradigms and principles.
2001,
Pubmed
Ingham,
Patched represses the Hedgehog signalling pathway by promoting modification of the Smoothened protein.
2000,
Pubmed
Jessell,
Neuronal specification in the spinal cord: inductive signals and transcriptional codes.
2000,
Pubmed
Lawrence,
hedgehog and engrailed: pattern formation and polarity in the Drosophila abdomen.
1999,
Pubmed
Lawrence,
The hedgehog morphogen and gradients of cell affinity in the abdomen of Drosophila.
1999,
Pubmed
Lee,
The specification of dorsal cell fates in the vertebrate central nervous system.
1999,
Pubmed
Lee,
Autoproteolysis in hedgehog protein biogenesis.
1994,
Pubmed
Lewis,
Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1.
2001,
Pubmed
,
Xenbase
Liem,
A role for the roof plate and its resident TGFbeta-related proteins in neuronal patterning in the dorsal spinal cord.
1997,
Pubmed
,
Xenbase
Liem,
Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites.
2000,
Pubmed
Litingtung,
Specification of ventral neuron types is mediated by an antagonistic interaction between Shh and Gli3.
2000,
Pubmed
,
Xenbase
Litingtung,
Shh and Gli3 are dispensable for limb skeleton formation but regulate digit number and identity.
2002,
Pubmed
Marigo,
Biochemical evidence that patched is the Hedgehog receptor.
1996,
Pubmed
,
Xenbase
Marigo,
Regulation of patched by sonic hedgehog in the developing neural tube.
1996,
Pubmed
McMahon,
Developmental roles and clinical significance of hedgehog signaling.
2003,
Pubmed
Ming,
Human developmental disorders and the Sonic hedgehog pathway.
1998,
Pubmed
,
Xenbase
Morata,
Control of compartment development by the engrailed gene in Drosophila.
1975,
Pubmed
Ohlmeyer,
Hedgehog stimulates maturation of Cubitus interruptus into a labile transcriptional activator.
,
Pubmed
Park,
Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation.
2000,
Pubmed
,
Xenbase
Patten,
Opponent activities of Shh and BMP signaling during floor plate induction in vivo.
2002,
Pubmed
Pearse,
Ptc1 and Ptc2 transcripts provide distinct readouts of Hedgehog signaling activity during chick embryogenesis.
2001,
Pubmed
Pepinsky,
Identification of a palmitic acid-modified form of human Sonic hedgehog.
1998,
Pubmed
Persson,
Dorsal-ventral patterning of the spinal cord requires Gli3 transcriptional repressor activity.
2002,
Pubmed
,
Xenbase
Pierani,
A sonic hedgehog-independent, retinoid-activated pathway of neurogenesis in the ventral spinal cord.
1999,
Pubmed
Porter,
The product of hedgehog autoproteolytic cleavage active in local and long-range signalling.
1995,
Pubmed
Porter,
Hedgehog patterning activity: role of a lipophilic modification mediated by the carboxy-terminal autoprocessing domain.
1996,
Pubmed
Porter,
Cholesterol modification of hedgehog signaling proteins in animal development.
1996,
Pubmed
Rietveld,
Association of sterol- and glycosylphosphatidylinositol-linked proteins with Drosophila raft lipid microdomains.
1999,
Pubmed
Robertson,
Derivation and maintenance of embryonic stem cell cultures.
1997,
Pubmed
Rodriguez,
Control of compartmental affinity boundaries by hedgehog.
1997,
Pubmed
Sander,
Ventral neural patterning by Nkx homeobox genes: Nkx6.1 controls somatic motor neuron and ventral interneuron fates.
2000,
Pubmed
Schaeren-Wiemers,
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,
Pubmed
Stone,
The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog.
1996,
Pubmed
Strutt,
Mutations in the sterol-sensing domain of Patched suggest a role for vesicular trafficking in Smoothened regulation.
2001,
Pubmed
Theil,
Gli3 is required for Emx gene expression during dorsal telencephalon development.
1999,
Pubmed
,
Xenbase
Tsuchida,
Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes.
1994,
Pubmed
Wang,
Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb.
2000,
Pubmed
,
Xenbase
Wilkinson,
Detection of messenger RNA by in situ hybridization to tissue sections and whole mounts.
1993,
Pubmed
Yamada,
Control of cell pattern in the developing nervous system: polarizing activity of the floor plate and notochord.
1991,
Pubmed
Zambrowicz,
Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells.
1997,
Pubmed
Zeng,
A freely diffusible form of Sonic hedgehog mediates long-range signalling.
2001,
Pubmed
Zhang,
Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R asymmetry by the mouse node.
2001,
Pubmed
,
Xenbase
