Reduction in the activity of the a-melanocyte-stimulating hormone (a-MSH) system causes obesity, and infusions of a-MSH can produce satiety, raising the possibility that a-MSH may mediate physiological satiety signals. Since a-MSH is coded for by the pro-opiomelanocortin (POMC) gene, we examined if POMC gene expression would be inhibited by fasting in normal mice or in models of obesity characterized by leptin insufficiency (ob/ob} or leptin insensitivity (dfe/db). In wild-type mice, hypothalamic POMC mRNA was decreased >60% after a 2-day fast and was positively correlated with leptin mRNA. Similarly, compared with controls, POMC mRNA was decreased by at least 60% in both db/db and ob/ob mice. POMC mRNA was negatively correlated with both neuropeptide Y (NPY) and melanin-concentrating hormone (MCH) mRNA. Finally, treatment of both male and female ob/ob mice with leptin stimulated hypothalamic POMC mRNA by about threefold. These results suggest that impairment in production, processing, or responsiveness to a-MSH may be a common feature of obesity and that hypothalamic POMC neurons, stimulated by leptin, may constitute a link between leptin and the melanocortin system. Diabetes 47:294-297, 1997

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Mutations in the obese (ob)

Neuronal migration is a fundamental process in central nervous system (CNS) development. The assembly of functioning neuronal circuits relies on neuronal migration occurring in the appropriate spatio-temporal pattern. A defect in the neuronal migration may result in a neurological disorder. The cerebellum, as a part of the CNS, plays a pivotal role in motor coordination and non-motor functions such as emotion, cognition and language. The excitatory and inhibitory neurons within the cerebellum originate from different distinct germinal zones and migrate through complex routes to assemble in a well-defined neuronal organization in the cerebellar cortex and nuclei. In this review article, the neuronal migration modes and pathways from germinal zones to the final position in the cerebellar cortex and nuclei will be described. The cellular and molecular mechanisms involved in cerebellar neuronal migration during development will also be reviewed. Finally, some diseases and animal models associated with defects in neuronal migration will be presented.

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