PUBLICATION
Repression of the hindbrain developmental program by Cdx factors is required for the specification of the vertebrate spinal cord
- Authors
- Skromne, I., Thorsen, D., Hale, M., Prince, V.E., and Ho, R.K.
- ID
- ZDB-PUB-070523-17
- Date
- 2007
- Source
- Development (Cambridge, England) 134(11): 2147-2158 (Journal)
- Registered Authors
- Hale, Melina, Ho, Robert K., Prince, Victoria E., Skromne, Isaac
- Keywords
- Cdx, Caudal, Hox, Retinoic acid, Segmentation, Rhombomeres, Hindbrain, Spinal cord, Central nervous system, Chordates, Vertebrates, Evolution
- MeSH Terms
-
- Animals
- Cell Differentiation/physiology*
- Cell Transplantation
- DNA Primers/genetics
- Ectoderm/cytology
- Ectoderm/metabolism
- Homeodomain Proteins/metabolism*
- Immunohistochemistry
- In Situ Hybridization
- Microscopy, Fluorescence
- Morphogenesis/physiology*
- Rhombencephalon/embryology*
- Rhombencephalon/metabolism
- Spinal Cord/embryology*
- Spinal Cord/metabolism
- Zebrafish/embryology*
- Zebrafish Proteins/metabolism*
- PubMed
- 17507415 Full text @ Development
Citation
Skromne, I., Thorsen, D., Hale, M., Prince, V.E., and Ho, R.K. (2007) Repression of the hindbrain developmental program by Cdx factors is required for the specification of the vertebrate spinal cord. Development (Cambridge, England). 134(11):2147-2158.
Abstract
The spinal cord is a unique vertebrate feature that originates, together with the hindbrain, from the caudal neural plate. Whereas the hindbrain subdivides into rhombomeres, the spinal cord remains unsegmented. We have identified Cdx transcription factors as key determinants of the spinal cord region in zebrafish. Loss of Cdx1a and Cdx4 functions causes posterior expansion of the hindbrain at the expense of the unsegmented spinal cord. By contrast, cdx4 overexpression in the hindbrain impairs rhombomere segmentation and patterning and induces the expression of spinal cord-specific genes. Using cell transplantation, we demonstrate that Cdx factors function directly within the neural ectoderm to specify spinal cord. Overexpression of 5' Hox genes fails to rescue hindbrain and spinal cord defects associated with cdx1a/cdx4 loss-of-function, suggesting a Hox-independent mechanism of spinal cord specification. In the absence of Cdx function, the caudal neural plate retains hindbrain characteristics and remains responsive to surrounding signals, particularly retinoic acid, in a manner similar to the native hindbrain. We propose that by preventing the posterior-most region of the neural plate from following a hindbrain developmental program, Cdx factors help determine the size of the prospective hindbrain and spinal cord territories.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping