Delta-like 1 Homologue is a Hypothalamus-Enriched Protein that is Present in Orexin-Containing Neurones of the Lateral Hypothalamic Area

Delta-like 1 homologue (DLK1), also known as preadipocyte factor-1, fetal antigen 1 or pG2, is a transmembrane protein belonging to the epidermal growth factor-like superfamily. The protein becomes soluble and biologically active after cleavage of the tumour necrosis factor--converting enzyme. DLK1 is involved in the differentiation of several cell types, including adipocytes. Lack of the dlk1 gene in mice results in adiposity and a polymorphism within the gene encoding DLK1 has been associated with obesity. The dlk1 gene is expressed in restricted areas of the central nervous system with an enrichment of cell bodies expressing DLK1 mRNA in the hypothalamus. Goat and rabbit antisera to DLK1 were used to study the cellular localisation and chemical identity of DLK1-immunoreactive neuronal cell bodies in rat hypothalamus. DLK1 immunoreactivity was demonstrated in the cell bodies of the suprachiasmatic, supraoptic, paraventricular, arcuate nuclei and in the lateral hypothalamus. At the subcellular level, DLK1 immunoreactivity was observed in the cell soma and dendrites, although not in axonal fibres or nerve terminals. Double-labelling of sections from the lateral hypothalamic/perifornical area of colchicine-treated rats (a treatment that increases the content of immunoreactive material in the cell soma) showed that DLK1 was present in the virually all orexin- and dynorphin-containing neurones. By contrast, DLK1 was not demonstrated in any melanin-concentrating hormone or cocaine- and amphetamine-regulated transcript-containing neurones of the lateral hypothalamic/perifornical area. The presence of DLK1 in a population of lateral hypothalamic neurones suggests a functional role for DLK1 in orexin/hypocretin/dynorphin neurones.