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Abstract
Cited2 is a member of the CITED gene family of transcriptional co-factors widely expressed in the mouse conceptus. It interacts with various transcriptional factors to drive the proper development of many organs in the mouse. Territories of Cited2 expression in the mouse coincide with the tissues most affected in Cited2 null mice. Embryos deficient in Cited2 display complex heart defects that may have multiple origins. One possibility is that the establishment of the left-right body axis that provide morphological cues for developing organs, like the heart, is perturbed in these mutant embryos. Cited2 is expressed in the relevant left-right patterning tissues such as the node and the lateral plate mesoderm. Therefore, the biochemical role Cited2 plays in left-right patterning was explored. This part of the study provides insight into how Cited2 may function in left-right development and organogenesis.
Cited2 is also very important in the developing mouse placenta, where it is expressed in many trophoblast subtypes and vascular cells. Cited2 deficient placentas are grossly small in size, with reduced trophoblast numbers and an expanded foetal vasculature. This part of the study further characterised the cellular expression of Cited2 in placental cells. It also further describes the vascular phenotype in Cited2 mutants, and biochemically relevant molecules to inform on the potential molecular workings of the phenotype. Furthermore, conditional deletion of Cited2 was also performed to understand which placental compartments Cited2 is primarily required. It was found that endothelial cell-specific deletion of Cited2 phenocopied much of the complete Cited2 null placental phenotype, indicating that Cited2 is necessary in endothelial cells of the mouse placenta.