Populations of self-renewing cells that arise during normal embryonic development harbour the potential for rapid proliferation, migration or transdifferentiation and, therefore, tumour generation. So, control mechanisms are essential to prevent rapidly expanding populations from malignant growth. Transcription factors have crucial roles in ensuring establishment of such regulation, with the Pax gene family prominent amongst these. This review examines the role of Pax family members during embryogenesis, and their contribution to tumorigenesis when subverted.

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AMG 386 has clinical activity and an acceptable safety profile both as monotherapy and in combination with chemotherapy. Of note, as the toxicity profiles of AMG 386 and inhibitors of the VEGF axis do not substantially overlap, AMG 386 could potentially be combined with other anti-angiogenic compounds to maximize disruption of malignant vascularization in ovarian cancer and other solid tumors.

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Abstract. Genomic imprinting confers allele-specific expression in less than 1% of genes, in a parent-of-origin specific fashion. In humans and mice the Peg1/Mest gene (Mest) is maternally repressed, and paternally expressed. Mest is expressed in embryogenic mesoderm-derived tissues and in adult brain, and paternal mutations in Mest lead to growth retardation and defective maternal behaviour. Despite our current understanding of mechanisms associated with the establishment of imprinting of Mest and other imprinted genes, it is unclear to what extent Mest imprinting needs to be maintained in adult tissues. Aberrations of imprinting are known to occur in certain rare syndromes, and involve either inherited mutations, or constitutive epigenetic alterations occurring soon after fertilization. Imprinting abnormalities may also occur in the aging somatic tissues of adult individuals. Here we report an occurrence of post-embryonic somatic variability of Mest allelic expression in a colony of mice where heterozygotes at the imprinted Mest locus for a mutation inherited from the father spontaneously expressed the normally silenced allele from the mother. In addition, a newly acquired ability to overcome the deficit in maternal reproductive behaviour had occurred in the mutant mice, but this appeared not to be directly linked to the Mest mutation. Our results suggest that at least one allele of Mest expression is required in the somatic tissues of adult individuals and that under certain conditions (such as in the presence of a Mest insertional mutation or in an altered genetic background), somatically acquired alterations of allelic expression at the Mest locus may occur. Key words: Adult brain expression, Epigenetic, Imprinting, Maternal behaviour, Somatic expression, Peg1/Mest (J. Reprod. Dev. 58: [490][491][492][493][494][495][496][497][498][499][500] 2012) I n mammals the mesoderm-specific locus, Paternally expressed gene 1 (Peg1/Mest; hereafter called Mest), transcribes a maternally imprinted gene expressed in the mesoderm lineage during embryogenesis, and in adult tissues, such as brain [1]. The precise function of Mest is unknown, although its gene product has similarity to the α/β hydrolase family of proteins [2]. Knock out studies in mice show that Mest is important for proper tissue growth and adult maternal reproductive behaviour [3]. Mest +/tm1Lef heterozygous mutant mice carrying a non-functional paternally inherited mutant allele (denoted here as Mest +/-) display retarded growth, and in females a reduction of their reproductive fitness caused by failure to nurture or care for pups [3], whereas conversely heterozygous mutant mice with the maternally inherited mutant allele Mest tm1Lef/+ (denoted here as Mest -/+ ) are normal, because Mest is a paternally expressed gene.While reproductive fitness is an important trait for species survival, relatively little is known about the role of genomic imprinting in reproductive fitness. Stochastic errors of imprinting or other spontaneous imprinting epimutations, s...