title: Role of homeobox genes in the hypothalamic development and energy balance.
abstract: Homeobox genes contribute to the regionalization, patterning and cell differentiation during embryogenesis and organ development. During mammalian embryonic development, homeobox genes, including orthopedia (Otp), a brain-specific homeobox transcription factor (Bsx) and a thyroid transcription factor-1 (TTF-1), are expressed in the hypothalamus. The genetic ablation of these genes indicated that Otp and TTF-1 are essential for the normal morphological development of the hypothalamus, including the arcuate nucleus (ARC), whereas Bsx is not required. In the adult stage, Bsx and TTF-1 continue to be expressed in the hypothalamus, including the ARC, and serve as transcription factors of neuropeptide Y and agouti-related protein. The expression of hypothalamic Bsx and TTF-1 can be altered by the feeding state and appetite regulatory hormones such as ghrelin and leptin. Although Bsx and TTF-1 are essential for normal feeding behavior in adult mice, they exert different effects on the expression of hypothalamic pro-opiomelanocortin (POMC) and body weight homeostasis. Thus, the hypothalamic homeobox genes may contribute to the dissociation of food intake and body weight via AgRP-POMC neurons.
authors.affiliation: Department of Lifestyle Medicine, Translational Research Center, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kaji
authors.forename: Katsunori
authors.initials: K
authors.lastname: Nonogaki
mesh_terms: D054369:Agouti-Related Protein / Q000235:genetics / Q000502:physiology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000196:embryology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics; D005801:Genes, Homeobox / Q000502:physiology*; D054439:Ghrelin / Q000502:physiology; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D007031:Hypothalamus / Q000196:embryology* / Q000502:physiology*; D020738:Leptin / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009478:Neuropeptide Y / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000235:genetics; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; C492588:Bsx protein, mouse; D004268:DNA-Binding Proteins; D054439:Ghrelin; D018398:Homeodomain Proteins; D020738:Leptin; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; C088624:Otp protein, mouse; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C504004:Ttf1 protein, mouse; D011333:Pro-Opiomelanocortin