Differential requirements for neurogenin 3 in the development of POMC and NPY neurons in the hypothalamus

• Published in: Developmental biology 2011-01, Vol.349 (2), p.406-416
• Main Authors: Pelling, Michelle, Anthwal, Neal, McNay, David, Gradwohl, Gerard, Leiter, Andrew B., Guillemot, Francois, Ang, Siew-Lan
• Format: Article
• Language: English
• Subjects: Animals; Arcuate nucleus; basic helix-loop-helix transcription factors; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; energy; Energy Metabolism - genetics; Energy Metabolism - physiology; food intake; homeostasis; hypothalamus; Hypothalamus - embryology; Immunohistochemistry; In Situ Hybridization; Indoles; Life Sciences; Mice; Mice, Knockout; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; neurogenesis; Neurogenesis - genetics; Neurogenesis - physiology; Neuronal identity; neurons; Neurons - metabolism; Neuropeptide Y - metabolism; Ngn3; NPY; obesity; POMC; population; Pro-Opiomelanocortin - metabolism; Ventral hypothalamus
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2010.11.007

The neuroendocrine hypothalamus regulates a spectrum of essential biological processes and underlies a range of diseases from growth failure to obesity. While the exploration of hypothalamic function has progressed well, knowledge of hypothalamic development is poor. In particular, very little is known about the processes underlying the genesis and specification of the neurons in the arcuate and ventromedial nuclei. Recent studies demonstrate that the proneural basic helix-loop-helix transcription factor Mash1 is required for neurogenesis and neuronal subtype specification in the ventral hypothalamus. We demonstrate here that Ngn3, another basic helix-loop-helix transcription factor, is expressed in mitotic progenitors in the arcuate and ventromedial hypothalamic regions of mouse embryos from embryonic days 9.5–17.5. Genetic fate mapping and loss of function studies in mice demonstrate that Ngn3+ progenitors contribute to subsets of POMC, NPY, TH and SF1 neurons and is required for the specification of these neuronal subtypes in the ventral hypothalamus. Interestingly, while Ngn3 promotes the development of arcuate POMC and ventromedial SF1 neurons, it inhibits the development of NPY and TH neurons in the arcuate nuclei. Given the opposing roles of POMC and NPY neurons in regulating food intake, these results indicate that Ngn3 plays a central role in the generation of neuronal populations controlling energy homeostasis in mice. ► We studied the role of Ngn3 in the development of mouse ventral hypothalamic neurons. ► Ngn3+ neural progenitors contribute to NPY+, POMC+, SF1+ and TH+ neuronal populations. ► Reduced and increase numbers of POMC+ and NPY+ neurons respectively in Ngn3-/- embryos. ► No change in proneural gene expression or total cell number in Ngn3-/- embryos. ► Ngn3 plays a central role in the generation of neurons controlling energy balance.