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Hox genes control the specification of global vertebral domains
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The development of an animal from embryo to adult is an actively regulated process, largely controlled through differential gene expression. Hox genes are key modulators of embryonic development. Among other functions, they are essential for patterning the body plan by conferring identity to segments along the anterior-posterior axis. In vertebrates, Hox genes can specify the
identity of both individual vertebrae and global vertebral domains in the axial
skeleton. Hox group 10 is responsible for the layout of the lumbar region by
inhibiting rib formation, while Hox group 11 defines the sacral domain of the skeleton. It was previously thought that ribs were set out by default. Hence, it was suggested that another Hox gene would have to inhibit rib formation in the cervical domain, similarly to Hox group 10 in the caudal part of the
skeleton. We produced mice bearing ribs in every vertebrae by overexpressing
Hoxb6 in the PSM under the control of the Dll1 promoter, showing that the thoracic area is formed through the activity of Hox group 6 genes that specifically induce rib formation, and that the cervical domain is
defined as the area that precedes Hox group 6 expression. In this study, we used our two Hox over-expression mouse models with complementary rib phenotypes to study the molecular mechanisms of rib development.(...)
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Dissertação apresentada para obtenção do grau de doutor em Biologia pelo Instituto de Tecnologia Química e Biológica da
Universidade Nova de Lisboa
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Universidade Nova de Lisboa, Instituto de Tecnologia Química e Biológica