Kettleborough, Ross; (2003) The isolation and characterisation of the novel gene C53. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The study of axis formation is crucial if we are to understand the formation of a functional body plan. In mouse, the first morphological marker of A-P pattern, the primitive streak, forms at the posterior of the embryo and drives a complex process called gastrulation, during which new germ layers are formed and a general body plan is generated that serves as a scaffold for the subsequent morphogenesis of the embryo. In order to isolate tissue specific genes that are involved in these symmetry breaking events a cDNA library derived from the endoderm of the 7.5dpc mouse embryo was produced. A screen was then performed that used sequence and expression information to further analyse the endoderm specific library. cDNA clones representing genes that are expressed in tissues intimately involved in the early patterning of the embryo (e.g. the visceral endoderm, the definitive endoderm and the node) were identified. This study focuses on C53, a novel gene that is expressed in the visceral endoderm, the node, and hematopoietic lineages of the early mouse embryo. A targeted mutation has been generated that results in homozygous null animals and causes embryonic lethality after 14.5dpc from severe anemia. In vitro differentiation of C53 null ES cells indicates that a de-regulation of hematopoietic transcription factors occurs when C53 is not present, and further analysis has shown that hematopoietic specific molecules are inappropriately expressed in the embryonic yolk sac and embryonic liver. This investigation indicates that the novel gene C53 is essential for the correct differentiation of certain hematopoietic lineages.

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