Homeobox gene Sax2 deficiency causes an imbalance in energy homeostasis.
The brain, in particular the hypothalamus and the brainstem, plays a critical role in the regulation of energy homeostasis by incorporating signals from the periphery and translating them into feeding behavior. Here we show that the homeobox gene Sax2, which is expressed predominantly in the brainstem, in the vicinity of serotonergic neurons, contributes to this physiological balance. Sax2 deficiency results in a decrease of fat and glycogen storage, reduced blood glucose levels, and raised serotonin levels in the hindbrain. Surprisingly, in the brainstem the expression levels of pro-opiomelanocortin and neuropeptide Y were indicative of a fasting condition, opposed to the observed high serotonin levels implying satiation. Furthermore, Sax2-directed lacZ expression reveals a dramatic change of the distribution of Sax2-expressing cells in the null mutant occurring during perinatal development. These data strongly suggest that Sax2 is required for the coordinated crosstalk of factors involved in the maintenance of energy homeostasis.
Simon
Ruth
R
Department of Pathology, Mount Sinai School of Medicine, New York, New York 10029, USA. ruth.simon@mssm.edu
Lufkin
Thomas
T
Bergemann
Andrew D
AD
D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics*; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006706:Homeostasis; D051379:Mice; D008817:Mice, Mutant Strains; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D018398:Homeodomain Proteins; D009478:Neuropeptide Y; C109095:Nkx1-2 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D012701:Serotonin; D011333:Pro-Opiomelanocortin