title: Differential susceptibility of midbrain and spinal cord patterning to floor plate defects in the talpid2 mutant.
abstract: The chick talpid2 mutant displays polydactylous digits attributed to defects of the Hedgehog (HH) signaling pathway. We examined the talpid2 neural tube and show that patterning defects in the spinal cord and the midbrain are distinct from each other and from the limb. Unlike the Sonic Hedgehog (SHH) source in the limb, the SHH-rich floor plate (FP) is reduced in the talpid2 midbrain. This is accompanied by a severe depletion of medial cell populations that encounter high concentrations of SHH, an expansion of lateral cell populations that experience low concentrations of SHH and a broad deregulation of HH's principal effectors (PTC1, GLI1, GLI2, GLI3). Together with the failure of SHH misexpression to rescue the talpid2 phenotype, these results suggest that talpid2 is likely to have a tissue-autonomous, bidirectional (positive and negative) role in HH signaling that cannot be attributed to the altered expression of several newly cloned HH pathway genes (SUFU, DZIP1, DISP1, BTRC). Strikingly, FP defects in the spinal cord are accompanied by relatively normal patterning in the talpid2 mutant. We propose that this differential FP dependence may be due to the prolonged apposition of the notochord to the spinal cord, but not the midbrain during development.
authors.affiliation: Section of Neurobiology, University of Texas at Austin, Austin, TX 78712-0248, USA. agarwala@mail.utexas.edu
authors.forename: Seema
authors.initials: S
authors.lastname: Agarwala
authors.forename: Galina V
authors.initials: GV
authors.lastname: Aglyamova
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Marma
authors.forename: John F
authors.initials: JF
authors.lastname: Fallon
authors.forename: Clifton W
authors.initials: CW
authors.lastname: Ragsdale
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D030161:Avian Proteins / Q000235:genetics*; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D002642:Chick Embryo; D015536:Down-Regulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D020022:Genetic Predisposition to Disease; D053823:Hedgehog Proteins; D008636:Mesencephalon / Q000196:embryology*; D009436:Neural Tube Defects / Q000235:genetics; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics; D013116:Spinal Cord / Q000196:embryology*; D015534:Trans-Activators / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D030161:Avian Proteins; D053823:Hedgehog Proteins; D015534:Trans-Activators