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Ikaros is expressed in developing striatal neurons and involved in enkephalinergic differentiation
Author(s) -
Agoston Denes V.,
Szemes Marianna,
Dobi Albert,
Palkovits Miklos,
Georgopoulos Katia,
Gyorgy Andrea,
Ring Mary A.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04653.x
Subject(s) - striatum , biology , enkephalin , microbiology and biotechnology , gene expression , gene , regulation of gene expression , gene isoform , genetics , neuroscience , receptor , dopamine , opioid
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.