A NOVEL MAMMALIAN WNT GENE, WNT8B, SHOWS BRAIN-RESTRICTED EXPRESSION IN EARLY DEVELOPMENT, WITH SHARPLY DELIMITED EXPRESSION BOUNDARIES IN THE DEVELOPING FOREBRAIN

Our current knowledge of mammalian forebrain development is meagre. Th e comparatively few relevant anatomical landmarks are, however, being supplemented by gene expression studies which are able to identify sub sets of anatomical structures. We previously described cloning, subchr omosomal localization and preliminary structural characterization of t he human WNT8B gene, the first mammalian Wnt8b gene to be reported. Wn t genes encode intercellular signalling molecules which play a variety of critical roles in early development, including, in several cases, a presumed role in brain development. In the current report we present the full-length cDNA sequence and genomic organization of the human W nt8b gene and report studies of expression of the Wnt8b gene in human and mouse embryos. The human and mouse expression patterns appeared id entical and were restricted to the developing brain, with the great ma jority of expression being found in the developing forebrain. In the l atter case expression was confined to the germinative neuroepithelium of three sharply delimited regions: the dorsomedial wall of the telenc ephalic ventricles (which includes the developing hippocampus), a disc rete region of the dorsal thalamus and the mammillary and retro-mammil lary regions of the posterior hypothalamus. Expression in the developi ng hippocampus may suggest a role for WNT8B in patterning of this regi on and subchromosomal localization of the human gene to 10q24 may sugg est it as a candidate gene for partial epilepsy in families where the disease has been linked to markers in this region.