دورية أكاديمية
BMP receptor 1A regulates development of hypothalamic circuits critical for feeding behavior.
| العنوان: | BMP receptor 1A regulates development of hypothalamic circuits critical for feeding behavior. |
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| المؤلفون: | Peng CY; Department of Neurology, Northwestern University's Feinberg School of Medicine, Chicago, Illinois 60611, USA. c-peng@northwestern.edu, Mukhopadhyay A, Jarrett JC, Yoshikawa K, Kessler JA |
| المصدر: | The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2012 Nov 28; Vol. 32 (48), pp. 17211-24. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Print Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington, DC : Society for Neuroscience Original Publication: [Baltimore, Md.] : The Society, c1981- |
| مواضيع طبية MeSH: | Bone Morphogenetic Protein Receptors, Type I/*genetics , Feeding Behavior/*physiology , Hypothalamus/*metabolism , Nerve Net/*metabolism , Neurons/*metabolism, Agouti-Related Protein/metabolism ; Animals ; Bone Morphogenetic Protein Receptors, Type I/metabolism ; Cell Proliferation ; Feeding Behavior/drug effects ; Hypothalamus/drug effects ; Leptin/pharmacology ; Mice ; Mice, Knockout ; Nerve Net/drug effects ; Neural Pathways/drug effects ; Neural Pathways/metabolism ; Neurons/drug effects ; Neuropeptide Y/metabolism ; Signal Transduction/drug effects |
| مستخلص: | Hypothalamic neural circuits are known to regulate energy homeostasis and feeding behavior, but how these circuits are established during development is not well understood. Here we report that embryonic neural progenitors that express the transcription factor OLIG1 contribute neurons to the ventral hypothalamus including the arcuate nucleus (ARH), a center that regulates feeding behavior. Ablation of bone morphogenetic protein receptor 1a (BMPR1A) in the OLIG1 lineage resulted in hypophagia, hypoglycemia, and weight loss after the second postnatal week with death by week 4. Differentiation and specification of inhibitory hypothalamic neurons contributing to melanocortin and dopaminergic systems were abnormal in the BMPR1A-deficient ARH. Although the hypophagia promoted expression of the orexigenic neuropeptide agouti related protein (AgRP) in the BMPR1A-deficient ARH, there was a profound decrease of AgRP(+) axonal terminals in the mutant ARH targets including dorsomedial and paraventricular hypothalamic nuclei. Projection of AgRP(+) neurons to these nuclei is known to be regulated by leptin. Leptin injection in neonatal mice increased bone morphogenic protein (BMP) signaling in the ventral hypothalamus, and blocking BMP signaling prevented leptin-induced neurite outgrowth in ARH explant cultures. These findings suggest that BMPR1A signaling is critical for postnatal establishment of leptin-responsive orexigenic fibers from ARH to multiple hypothalamic nuclei. More generally these observations indicate that BMPR1A signaling regulates postnatal establishment of OLIG1 lineage-derived ARH neuronal circuits that are critical for leptin-mediated feeding behavior. |
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| معلومات مُعتمدة: | NS 20778 United States NS NINDS NIH HHS; R01 NS020778 United States NS NINDS NIH HHS; NS 20013 United States NS NINDS NIH HHS; R01 NS020013 United States NS NINDS NIH HHS; U54 CA151880 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Agouti-Related Protein) 0 (Leptin) 0 (Neuropeptide Y) EC 2.7.11.30 (Bone Morphogenetic Protein Receptors, Type I) |
| تواريخ الأحداث: | Date Created: 20121201 Date Completed: 20130219 Latest Revision: 20211021 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC3589760 |
| DOI: | 10.1523/JNEUROSCI.2484-12.2012 |
| PMID: | 23197713 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1529-2401 |
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| DOI: | 10.1523/JNEUROSCI.2484-12.2012 |