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First published online May 16, 2007
doi: 10.1242/10.1242/dev.002980

Development 134, 2147-2158 (2007)
Published by The Company of Biologists 2007
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Repression of the hindbrain developmental program by Cdx factors is required for the specification of the vertebrate spinal cord

Isaac Skromne*, Dean Thorsen, Melina Hale, Victoria E. Prince and Robert K. Ho

Department of Organismal Biology and Anatomy, The University of Chicago, 1027 E. 57th Street R107, Chicago, IL 60637, USA.

* Author for correspondence (e-mail: iskromne{at}uchicago.edu)

Accepted 29 March 2007

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.

Key words: Cdx, Caudal, Hox, Retinoic acid, Segmentation, Rhombomeres, Hindbrain, Spinal cord, Central nervous system, Chordates, Vertebrates, Evolution




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