Ikaros is expressed in developing striatal neurons and involved in enkephalinergic differentiation.
The Ikaros (Ik) gene encodes alternatively spliced zinc-finger proteins originally identified in developing hematopoietic organs and acts as master regulator of lymphoid development. During our search for transcription factors that control the developmental expression of the enkephalin (ENK) gene we found that Ik-1 and Ik-2 isoforms are specifically expressed in the embryonic striatum and bind the Ik-like cis-regulatory DNA element present on the ENK gene. Ik proteins are expressed by both proliferating (BrdU+/nestin+) and by post-mitotic differentiating (MAP2+) cells in the developing striatum between embryonic day 12 and post-natal day 2 and mRNAs encoding for the Ik and ENK genes are co-expressed by a subset of differentiating striatal neurons. Blocking the DNA binding of Ik proteins in differentiating embryonic striatal neuronal cultures resulted in decreased ENK expression and mutant animals lacking the DNA-binding domain of Ik had a deficit in the number of ENK but not in dynorphin or substance P mRNA+ cells. Animals lacking the protein interaction domain of Ik showed no deficit. These results demonstrate that Ik-1 and Ik-2 proteins through their DNA binding act as positive regulators of ENK gene expression in the developing striatum and participate in regulating enkephalinergic differentiation.
Agoston
Denes V
DV
Department of Anatomy, Physiology and Genetics, USUHS, Bethesda, Maryland, USALCB, NIMH, NIH, Bethesda, Maryland, USACutaneous Biology Research Center, MGH, Harvard Medical School, Charlestown, Massachusetts, USAGraduate Program in Genetics, The George Washington University, Washington, District of Columbia, USA.
Szemes
Marianna
M
Department of Anatomy, Physiology and Genetics, USUHS, Bethesda, Maryland, USALCB, NIMH, NIH, Bethesda, Maryland, USACutaneous Biology Research Center, MGH, Harvard Medical School, Charlestown, Massachusetts, USAGraduate Program in Genetics, The George Washington University, Washington, District of Columbia, USA.
Dobi
Albert
A
Department of Anatomy, Physiology and Genetics, USUHS, Bethesda, Maryland, USALCB, NIMH, NIH, Bethesda, Maryland, USACutaneous Biology Research Center, MGH, Harvard Medical School, Charlestown, Massachusetts, USAGraduate Program in Genetics, The George Washington University, Washington, District of Columbia, USA.
Palkovits
Miklos
M
Department of Anatomy, Physiology and Genetics, USUHS, Bethesda, Maryland, USALCB, NIMH, NIH, Bethesda, Maryland, USACutaneous Biology Research Center, MGH, Harvard Medical School, Charlestown, Massachusetts, USAGraduate Program in Genetics, The George Washington University, Washington, District of Columbia, USA.
Georgopoulos
Katia
K
Department of Anatomy, Physiology and Genetics, USUHS, Bethesda, Maryland, USALCB, NIMH, NIH, Bethesda, Maryland, USACutaneous Biology Research Center, MGH, Harvard Medical School, Charlestown, Massachusetts, USAGraduate Program in Genetics, The George Washington University, Washington, District of Columbia, USA.
Gyorgy
Andrea
A
Department of Anatomy, Physiology and Genetics, USUHS, Bethesda, Maryland, USALCB, NIMH, NIH, Bethesda, Maryland, USACutaneous Biology Research Center, MGH, Harvard Medical School, Charlestown, Massachusetts, USAGraduate Program in Genetics, The George Washington University, Washington, District of Columbia, USA.
Ring
Mary A
MA
Department of Anatomy, Physiology and Genetics, USUHS, Bethesda, Maryland, USALCB, NIMH, NIH, Bethesda, Maryland, USACutaneous Biology Research Center, MGH, Harvard Medical School, Charlestown, Massachusetts, USAGraduate Program in Genetics, The George Washington University, Washington, District of Columbia, USA.
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D003342:Corpus Striatum / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D051740:Ikaros Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism
D004268:DNA-Binding Proteins; D004745:Enkephalins; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor; D001973:Bromodeoxyuridine