H19 AND IGF2 ARE EXPRESSED AND DIFFERENTIALLY IMPRINTED IN NEUROECTODERM-DERIVED CELLS IN THE MOUSE-BRAIN

Igf2 and H19 are reciprocally imprinted genes that are closely linked and coexpressed in tissues of mesodermal and endodermal origin. Here w e report that coexpression of these genes is also found in specific fe tal tissues of neuroectodermal origin, that is in the ventral midline region of both the hindbrain and spinal cord. For cells of neuroectode rmal origin, complete absence of Igf2 and H19 transcription was previo usly described. Analysis of allele-specific expression of both Igf2 an d H19 in the ventral midline region of the hindbrain shows that H19 is expressed monoallelically, with the paternal allele being silent, whe reas Igf2 is expressed biallelically. Furthermore, we observed a stron g influence of the parental species background, in that the Mus muscul us allele was always expressed at higher levels than the M. spretus al lele. This was observed when the M. spretus allele was contributed by the mother or by the father. An analysis of Igf2 methylation by bisulp hite genomic sequencing provided no clear answer as to whether Igf2 ex pression and methylation are linked in a tissue of neuroectodermal ori gin. Taken together, our results provide novel information on H19 and Igf2 expression and imprinting patterns in the fetal mouse brain. In a ddition, they indicate that some aspects of Igf2 regulation in cells o f neuroectodermal origin do not follow the pattern that exists in meso derm- and endoderm-derived tissues. Apart from the ventral midline reg ion, H19 and Igf2 were found to be coexpressed in the ectodermally der ived Rathke's pouch and in some circumventricular organs of the brain, such as the organum vasculosum of the lamina terminalis (OVLT) and th e pineal gland.