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 ( DLK 1), also known as preadipocyte factor‐1, fetal antigen 1 or p G 2, 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‐α‐converting enzyme. DLK 1 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 DLK 1 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 DLK 1 m RNA in the hypothalamus. Goat and rabbit antisera to DLK 1 were used to study the cellular localisation and chemical identity of DLK 1‐immunoreactive neuronal cell bodies in rat hypothalamus. DLK 1 immunoreactivity was demonstrated in the cell bodies of the suprachiasmatic, supraoptic, paraventricular, arcuate nuclei and in the lateral hypothalamus. At the subcellular level, DLK 1 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 DLK 1 was present in the virually all orexin‐ and dynorphin‐containing neurones. By contrast, DLK 1 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 DLK 1 in a population of lateral hypothalamic neurones suggests a functional role for DLK 1 in orexin/hypocretin/dynorphin neurones.