Zic1 Promotes the Expansion of Dorsal Neural Progenitors in Spinal Cord by Inhibiting Neuronal Differentiation
| Autor: | Katsuhiko Mikoshiba, Jun Aruga, Shunsaku Homma, Takahide Tohmonda |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Genetic Markers
neuronal progenitors animal structures Molecular Sequence Data Mice Transgenic Bone Morphogenetic Protein 4 Chick Embryo Biology Bone morphogenetic protein ZIC1 neural development Mice bone morphogenetic protein medicine Animals Hedgehog Proteins dorsoventral patterning Sonic hedgehog Cloning Molecular neuronal differentiation Molecular Biology transcription factor Notch signaling Body Patterning Neurons Neuropeptides Neural tube Gene Expression Regulation Developmental Cell Differentiation Zinc Fingers Anatomy Cell Biology Spinal cord Zic Cell biology medicine.anatomical_structure Neurulation Spinal Cord GDF7 Bone Morphogenetic Proteins biology.protein Trans-Activators Neural development Transcription Factors Developmental Biology |
| Zdroj: | Developmental Biology. 244(2):329-341 |
| ISSN: | 0012-1606 |
| DOI: | 10.1006/dbio.2002.0598 |
| Popis: | The role of Zic1 was investigated by altering its expression status in developing spinal cords. Zic genes encode zinc finger proteins homologous to Drosophila Odd-paired. In vertebrate neural development, they are generally expressed in the dorsal neural tube. Chick Zic1 was initially expressed evenly along the dorsoventral axis and its expression became increasingly restricted dorsally during the course of neurulation. The dorsal expression of Zic1 was regulated by Sonic hedgehog, BMP4, and BMP7, as revealed by their overexpressions in the spinal cord. When Zic1 was misexpressed on the ventral side of the chick spinal cord, neuronal differentiation was inhibited irrespective of the dorsoventral position. In addition, dorsoventral properties were not grossly affected as revealed by molecular markers. Concordantly, when Zic1 was overexpressed in the dorsal spinal cord in transgenic mice, we observed hypercellularity in the dorsal spinal cord. The transgene-expressing cells were increased in comparison to those of truncated mutant Zic1-bearing mice. Conversely, we observed a significant cell number reduction without loss of dorsal properties in the dorsal spinal cords of Zic1-deficient mice. Taken together, these findings suggest that Zic1 controls the expansion of neuronal precursors by inhibiting the progression of neuronal differentiation. Notch-mediated inhibition of neuronal differention is likely to act downstream of Zic genes since Notch1 is upregulated in Zic1-overexpressing spinal cords in both the mouse and the chick. |
| Databáze: | OpenAIRE |
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