TRANSFERRIN AND ITS RECEPTOR IN THE DEVELOPMENT OF GENETICALLY-DETERMINED NEURAL-TUBE DEFECTS IN THE MOUSE EMBRYO

The iron-binding growth factor transferrin is taken up and localised i n the hindgut of midgestation mouse embryos. We investigated whether t he distribution of transferrin may be disturbed in mutant curly tail e mbryos, a proportion of which exhibit a cell proliferation defect affe cting the hindgut endoderm, as part of the pathogenetic sequence leadi ng to development of neural tube defects. Immunostaining revealed a re duction in the binding and/or uptake of transferrin by hindgut epithel ial cells in affected curly tail embryos compared with their unaffecte d littermates. There was no apparent difference between the two embryo types, however, in the distribution or level of expression of the tra nsferrin receptor. The receptor is expressed specifically in the hindg ut endoderm of the 10.5-day embryo, although its mRNA is present in al l tissues of the posterior neuropore region, suggesting posttranscript ional control of gene expression. These findings may indicate a role f or transferrin binding and/or uptake in the regulation of cell prolife ration in the hindgut endoderm, with a defect in this process in the c urly tail mutant. However, an alternative explanation is suggested by our finding that transferrin immunostaining is more intense in the hin dgut of unaffected curly tail embryos than in nonmutant CBA/Ca and CD- 1 embryos. Thus, mutant embryos may increase their uptake of transferr in in an attempt to compensate for defective cell proliferation in the hindgut resulting from a defect in another pathway. Only a proportion of embryos are able to mount this compensatory response leading to th e observed partial penetrance of developmental defects in the curly ta il mutant mouse. (C) 1996 Wiley-Liss, Inc.