The role of Caudal transcription factors during segmentation of the nervous system and paraxial mesoderm

Abstract

The segmental nature of the embryo is most evident within the paraxial mesoderm during the formation of somites and within the nervous system during the formation of hindbrain rhombomeres. Classic and modern embryological experiments show that the posterior neural plate gives rise to the hindbrain and spinal cord portions of the central nervous system. Then, the hindbrain is subdivided into neuromeres that are required for proper structural patterning of the adult brain stem while the spinal cord remains unsegmented, although able to receive signaling cues from the adjacent mesoderm to organize its neuronal populations into an iterative pattern. What sets up the difference between segmented and unsegmented regions? Here, we use genetic and molecular approaches in zebrafish to address the mechanisms involved in the determination of the hindbrain and spinal cord regions from a common posterior neural plate territory. In all species studied so far, including zebrafish, members of the Caudal (Cdx) family of homeobox transcription factors are required for proper development of the most posterior regions of the embryo. We examined hindbrain and spinal cord neuronal populations in zebrafish embryos lacking cdx1a and cdx4 activities. Single cdx1a or cdx4 depleted embryos show mild shifts in the distribution of these neuronal populations. In contrast, double cdx1a/cdx4-deficient embryos display the presence of hindbrain neuronal populations throughout the trunk and tail of the animal and the absence of spinal cordspecific neuronal markers. In addition, hox expression analysis in double mutants reveals the presence of extra neuromeres that are arranged in a mirror image duplication pattern to the native hindbrain segments. Our data suggest that members of the Cdx family of homeobox transcription factors are required to suppress segmentation of the posterior portion of the neural plate and thus allow the development of the spinal cord. We further suggest that a common mechanism involving cdx genes may play a role in the segmentation of both the nervous system and the paraxial mesoderm.