The zinc-finger transcriptional repressor Blimp1 (Prdm1) controls gene expression patterns during differentiation of B lymphocytes and regulates epigenetic changes required for specification of primordial germ cells. Blimp1 is dynamically expressed at diverse tissue sites in the developing mouse embryo, but its functional role remains unknown because Blimp1 mutant embryos arrest at E10.5 due to placental insufficiency. To explore Blimp1 activities at later stages in the embryo proper, here we used a conditional inactivation strategy. A Blimp1-Cre transgenic strain was also exploited to generate a fate map of Blimp1-expressing cells. Blimp1 plays essential roles in multipotent progenitor cell populations in the posterior forelimb, caudal pharyngeal arches, secondary heart field and sensory vibrissae and maintains key signalling centres at these diverse tissues sites. Interestingly, embryos carrying a hypomorphic Blimp1 gfp reporter allele survive to late gestation and exhibit similar, but less severe developmental abnormalities, whereas transheterozygous Blimp1 gfp/-embryos with further reduced expression levels, display exacerbated defects. Collectively, the present experiments demonstrate that Blimp1 requirements in diverse cell types are exquisitely dose dependent.

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A sinall proportion of fractures progress to non-union. Non-uiiioiis are routinely classified into two groups either hypertrophic or atrophic according to their radiological appearance. It is a coiiimon preconception that non-unions with a hypertrophic appearance on X-ray are biologically active and vascular with potential to heal given the correct stable environment. Atrophic nonunions are considered to be avascular aiid inert and will not heal even under the correct stable environment. Non-unions are either infected or aseptic. I n the present study, we tested the liypothesis that aseptic atrophic tion-uiiioiis are less vascular than aseptic hypertrophic lion-unions aiid healing fractures. Biopsies were taken from the fracture gap of patients with healing fractures. hypertrophic lion-unions aiid atrophic non-unions. A dual labelling technique was used with antibodies against CD3 1 (JC70) and Collagen IV. Blood vessels were quantified using a Chalkley point eyepiece graticule. There was no statistically significant difference in the median vessel count between the three fracture groups. These findings do not support tlie hypothesis that established atrophic fracture non-union are less vascular than hypertrophic non-unions or healing fractures.

Gentamicin, at high concentrations, as achieved following topical application, inhibits cell proliferation in vitro and, therefore, may be detrimental to the repair process in vivo.