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 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.
Original language | English (US) |
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Pages (from-to) | 206-220 |
Number of pages | 15 |
Journal | Developmental Biology |
Volume | 288 |
Issue number | 1 |
DOIs | |
State | Published - Dec 1 2005 |
Funding
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.).
Keywords
- Dopaminergic neurons
- Floor plate
- Midbrain
- Motor neurons
- Notochord
- Sonic Hedgehog
- Spinal cord
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
- Developmental Biology