TY - JOUR
T1 - Differential susceptibility of midbrain and spinal cord patterning to floor plate defects in the talpid2 mutant
AU - Agarwala, Seema
AU - Aglyamova, Galina V.
AU - Marma, Amanda K
AU - Fallon, John F.
AU - Ragsdale, Clifton W.
N1 - Funding Information:
We thank R. Bayly, J. Fogel, T. Sanders and J. Wallingford for critical comments, Jacqueline Pisenti at UC Davis for her help in supplying us with talpid 2 fertilized eggs and P. Beachy, P. Brickell, C. Cepko, D. Cleveland, G. Eichele, C. Fan, C. Goridis, M. Goulding, B. Houston, T. Jessell, A. Leutz, A. McMahon, G. Martin, C. Tabin and M. Wassef for DNA reagents. This research was supported by grants from the March of Dimes and the NIH (C.W.R.; J.F.F.) and from UT-Austin (S.A.).
PY - 2005/12/1
Y1 - 2005/12/1
N2 - 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 talpid 2 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.
AB - 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 talpid 2 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.
KW - Dopaminergic neurons
KW - Floor plate
KW - Midbrain
KW - Motor neurons
KW - Notochord
KW - Sonic Hedgehog
KW - Spinal cord
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U2 - 10.1016/j.ydbio.2005.09.034
DO - 10.1016/j.ydbio.2005.09.034
M3 - Article
C2 - 16246323
AN - SCOPUS:28244493511
SN - 0012-1606
VL - 288
SP - 206
EP - 220
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -