A second independent pathway for development of mesencephalic dopaminergic neurons requires Lmx1b.
We identified the LIM homeodomain transcription factor Lmx1b in the mesencephalic dopamine (mesDA) systems of embryos and adults. Analysis of spatiotemporal expression in Lmx1b null mutants and wild-type mice implicated a cascade involving Lmx1b in the early development of mesDA neurons. Although disruption of this cascade did not block induction of tyrosine hydroxylase (TH), a key enzyme in DA synthesis, or Nurr1, a nuclear hormone receptor, Lmx1b knockout mice failed to induce the mesDA-specific homeodomain gene Ptx3 in TH-positive neurons. Eventually, this small set of TH-positive neurons was lost during embryonic maturation. The data suggest that at least two molecular cascades operate during the specification of the mesDA system, one specifying neurotransmitter phenotype and another essential for other aspects of mesDA neuron differentiation.
Smidt
M P
MP
Section of Molecular Neuroscience, Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Medical Faculty, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
Asbreuk
C H
CH
Cox
J J
JJ
Chen
H
H
Johnson
R L
RL
Burbach
J P
JP
D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D017931:DNA Primers; D004268:DNA-Binding Proteins; D004298:Dopamine / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D000683:Serum Amyloid P-Component / Q000032:analysis / Q000235:genetics; D013378:Substantia Nigra / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism; D000099153:Pentraxins
D002097:C-Reactive Protein; D017931:DNA Primers; D004268:DNA-Binding Proteins; D004298:Dopamine; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger; D000683:Serum Amyloid P-Component; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase; D000099153:Pentraxins; C112149:LIM homeobox transcription factor 1 beta; C539882:NR4A2 protein, human; C539883:Nr4a2 protein, mouse; C539884:Nr4a2 protein, rat