Segmentation of the mammalian hindbrain is essential for the proper development of head structures. Loss of hindbrain segmentation can result in muscle, neuronal and skeletal defects. Hindbrain segmentation has also been proposed to be important in determining how muscles attach to skeletal elements in the head. In chicks, muscle connective tissue is attached to skeletal elements composed of populations of cells originating from the same hindbrain segment. In both humans and mice, mutations in a number of genes have been shown to result in cranial defects. However, cranial skeleto-muscular attachments in mutant mice and human patients have not been characterized. The cellular composition of cranial skeleto-muscular attachments in both wild type and mutant mice will be analyzed using the recently developed FLPe site-specific recombinase system. This system will allow heritable marking of specific populations of cells in the segmented hindbrain. During later development, the contribution hindbrain cells provide to cranial skeleto-muscular attachments in both wild type and mutant animals will be analyzed. Understanding how muscles attach to specific regions of skeletal elements that have no obvious anatomical landmarks is important for understanding how cranial skeleto-muscular attachments are retained during evolution. In addition, identifying genetic components responsible for cranial skeleto-muscular attachments is an essential first step in identifying proteins required for attaching muscles to skeletal structures.
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