Dlx-1 and Dlx-2 expression in the adult mouse brain: relationship to dopaminergic phenotypic regulation.
Expression of the homeodomain-containing transcription factors Dlx-1 and Dlx-2 in the lateral (LGE) and medial (MGE) ganglionic eminences, subpallial embryonic structures, is required for generation of telencephalic interneurons. LGE- and MGE-derived progenitors migrate and populate a number of forebrain structures, including the cortex, hippocampus, and olfactory bulb (OB). Previous reports focusing on embryogenesis of telencephalic neurons in Dlx-1 and Dlx-2 null mice suggested a specific role for these genes in expression of the OB dopamine (DA) phenotype. We have investigated whether these genes also are expressed in adult brain, especially in those pallial derivatives, such as the OB, hippocampus, and possibly cortex, where neurogenesis continues in adults. With a highly sensitive, nonradioactive in situ hybridization technique and both DLX-2 and pan DLX antisera, widespread expression of both genes was found in adult mouse fore- but not mid- or hindbrain. The adult unilateral naris closure paradigm was employed to establish a causative role for Dlx in regulating tyrosine hydroxylase (TH) expression; TH is the first enzyme in DA biosynthesis. TH mRNA, but not Dlx expression, was significantly down-regulated in the OB ipsilateral to closure. These findings suggest that Dlx-1 and -2 do not play a direct role in DA phenotypic differentiation and TH gene regulation in adult OB. The widespread expression of Dlx mRNA and protein in the adult brain suggests that these genes may have additional roles in mature animals.
Weill Medical College of Cornell University at The Burke Medical Research Institute, White Plains, New York 10605, USA.
Sachiko
S
Saino-Saito
Roseann
R
Berlin
Harriet
H
Baker
D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D001931:Brain Mapping; D002454:Cell Differentiation / Q000235:genetics; D004298:Dopamine / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D005801:Genes, Homeobox / Q000235:genetics; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D009434:Neural Pathways / Q000502:physiology; D009830:Olfactory Bulb / Q000254:growth & development / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D012683:Sensory Deprivation / Q000502:physiology; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine