Involvement of doublecortin-expressing cells in the arcuate nucleus in body weight regulation

Endocrinology. 2012 Jun;153(6):2655-64. doi: 10.1210/en.2011-1760. Epub 2012 Apr 4.


Hypothalamic functions, including feeding behavior, show a high degree of plasticity throughout life. Doublecortin (DCX) is a marker of plasticity and neuronal migration expressed in the hypothalamus. Therefore, we wanted to map the fate of DCX(+) cells in the arcuate nucleus (ARC) of the hypothalamus. For this purpose, we generated a BAC transgenic mouse line that expresses the inducible recombinase CreER(T2) under control of the DCX locus. Crossing this line with the Rosa26 or Ai14 reporter mouse lines, we found reporter(+) cells in the ARC upon tamoxifen treatment. They were born prenatally and expressed both DCX and the plasticity marker TUC-4. Immediately after labeling, reporter(+) cells had an enlarged soma that normalized over time, suggesting morphological remodeling. Reporter(+) cells expressed β-endorphin and BSX, neuronal markers of the feeding circuit. Furthermore, leptin treatment led to phosphorylation of STAT3 in reporter(+) cells in accordance with the concept that they are part of the feeding circuits. Indeed, we found a negative correlation between the number of reporter(+) cells and body weight and epididymal fat pads. Our data suggest that DCX(+) cells in the ARC represent a cellular correlate of plasticity that is involved in controlling energy balance in adult mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / cytology
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Body Weight / genetics*
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Energy Metabolism
  • Female
  • Gene Expression*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Immunohistochemistry
  • Leptin / pharmacology
  • Male
  • Mice
  • Mice, Transgenic
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity
  • Neurons / cytology
  • Neurons / metabolism
  • Neuropeptides / genetics*
  • Neuropeptides / metabolism
  • Phosphorylation / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism


  • Bsx protein, mouse
  • Dcx protein, mouse
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Homeodomain Proteins
  • Leptin
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • STAT3 Transcription Factor