Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak formation and early patterning of the mouse embryo

Background Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdhex4/5 huntingtin deficient embryos. Results In the absence of huntingtin, expression of nutritive genes appears normal but E7.0–7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury) and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE) are specified. Conclusion Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in Huntington's disease.

Within and without family in the Icelandic sagas

The Icelandic sagas reflect a deep social interest in the nature of family obligations. Narrative tension and drama often result from carefully plotted increases in competition between families,while considerable space is given over to family biographies and genealogical information. As a result, the saga authors’ conception of the historical seems closely bound to a desire to represent family life. In Gísla saga Súrssonar and Íslendinga saga, the representation of family life extends to the situation of internal family conflicts, when the strict ethical codes underpinning the centrality of family obligations seem to be complicated and perhaps even threatened by characters’ formation of stronger bonds outside the family. The portrayal of internal family conflicts in these two sagas enabled the authors to express complex and often conflicting ethical issues.

Young children as regenerative tissue donors : considering the need for legal reform in light of divergent ethical approaches

In Australia, young children who lack decision-making capacity can have regenerative tissue removed to treat another person suffering from a severe or life-threatening disease. While great good can potentially result from this as the recipient’s life may be saved, ethical unease remains over the ‘use’ of young children in this way. This paper examines the ethical approaches that have featured in the debate over the acceptability and limits of this practice, and how these are reflected in Australia’s legal regime governing removal of tissue from young children. This analysis demonstrates a troubling dichotomy within the Australia’s laws that requires decision-makers to adopt inconsistent ethical approaches depending on where a donor child is situated. It is argued that this inconsistency in approach warrants legal reform of this ethically sensitive issue.