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.

Correlates of Pedometer Use: Results from a Community-based Physical Activity Intervention Trial (10,000 Steps Rockhampton)

Background Pedometers have become common place in physical activity promotion, yet little information exists on who is using them. The multi-strategy, community-based 10,000 Steps Rockhampton physical activity intervention trial provided an opportunity to examine correlates of pedometer use at the population level. Methods Pedometer use was promoted across all intervention strategies including: local media, pedometer loan schemes through general practice, other health professionals and libraries, direct mail posted to dog owners, walking trail signage, and workplace competitions. Data on pedometer use were collected during the 2-year follow-up telephone interviews from random population samples in Rockhampton, Australia, and a matched comparison community (Mackay). Logistic regression analyses were used to determine the independent influence of interpersonal characteristics and program exposure variables on pedometer use. Results Data from 2478 participants indicated that 18.1% of Rockhampton and 5.6% of Mackay participants used a pedometer in the previous 18-months. Rockhampton pedometer users (n = 222) were more likely to be female (OR = 1.59, 95% CI: 1.11, 2.23), aged 45 or older (OR = 1.69, 95% CI: 1.16, 2.46) and to have higher levels of education (university degree OR = 4.23, 95% CI: 1.86, 9.6). Respondents with a BMI > 30 were more likely to report using a pedometer (OR = 1.68, 95% CI: 1.11, 2.54) than those in the healthy weight range. Compared with those in full-time paid work, respondents in 'home duties' were significantly less likely to report pedometer use (OR = 0.18, 95% CI: 0.06, 0.53). Exposure to individual program components, in particular seeing 10,000 Steps street signage and walking trails or visiting the website, was also significantly associated with greater pedometer use. Conclusion Pedometer use varies between population subgroups, and alternate strategies need to be investigated to engage men, people with lower levels of education and those in full-time 'home duties', when using pedometers in community-based physical activity promotion initiatives.