title: The atypical homeoprotein Pbx1a participates in the axonal pathfinding of mesencephalic dopaminergic neurons.
abstract: BACKGROUND
  The pre B-cell leukemia transcription factor 1 (Pbx1) genes belong to the three amino acid loop extension family of homeodomain proteins that form hetero-oligomeric complexes with other homeodomain transcription factors, thereby modulating target specificity, DNA binding affinity and transcriptional activity of their molecular associates.
  
  
  RESULTS
  Here, we provide evidence that Pbx1 is expressed in mesencephalic dopaminergic neurons from embryonic day 11 into adulthood and determines some of the cellular properties of this neuronal population. In Pbx1-deficient mice, the mesencephalic dopaminergic axons stall during mid-gestation at the border between di- and telencephalon before entering the ganglionic eminence, leading to a loose organization of the axonal bundle and partial misrouting. In Pbx1-deficient dopaminergic neurons, the high affinity netrin-1 receptor, deleted in colon cancer (DCC), is down-regulated. Interestingly, we found several conserved Pbx1 binding sites in the first intron of DCC, suggesting a direct regulation of DCC transcription by Pbx1.
  
  
  CONCLUSIONS
  The expression of Pbx1 in dopaminergic neurons and its regulation of DCC expression make it an important player in defining the axonal guidance of the midbrain dopaminergic neurons, with possible implications for the normal physiology of the nigro-striatal system as well as processes related to the degeneration of neurons during the course of Parkinson's disease.
authors: Laboratory of Molecular Neuropathology, Centre for Integrative Biology, University of Trento, Trento, Italy. sgado@science.unitn.it
authors: Paola
authors: P
authors: Sgadò
authors: Elisabetta
authors: E
authors: Ferretti
authors: Daniel
authors: D
authors: Grbec
authors: Yuri
authors: Y
authors: Bozzi
authors: Horst H
authors: HH
authors: Simon
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism*; D000075389:DCC Receptor; D059290:Dopaminergic Neurons / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism*; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000075386:Netrin Receptors; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011956:Receptors, Cell Surface / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000075389:DCC Receptor; C501910:Dcc protein, mouse; D018398:Homeodomain Proteins; D000075386:Netrin Receptors; C481797:Pbx1 protein, mouse; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins