Pomc-expressing progenitors give rise to antagonistic neuronal populations in hypothalamic feeding circuits

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Abstract
Proper body weight is determined by orexigenic and anorexigenic neurons in the hypothalamus. Lori Zeltser and her colleagues have found that a subset of neurons in the developing hypothalamus expressing a potent orexigenic hormone is derived from precursors expressing an anorexigenic hormone. These results suggest that developing feeding circuits are more plastic than previously thought and give rise to new concerns about the effects of a mother's diet during pregnancy on her offspring. Hypothalamic neuron circuits regulating energy balance are highly plastic and develop in response to nutrient and hormonal cues. To identify processes that might be susceptible to gestational influences in mice, we characterized the ontogeny of proopiomelanocortin (POMC) and neuropeptide Y (NPY) cell populations, which exert opposing influences on food intake and body weight. These analyses revealed that Pomc is broadly expressed in immature hypothalamic neurons and that half of embryonic Pomc-expressing precursors subsequently adopt a non-POMC fate in adult mice. Moreover, nearly one quarter of the mature NPY+ cell population shares a common progenitor with POMC+ cells.