Developmental restriction of the LIM homeodomain transcription factor Islet-1 expression to cholinergic neurons in the rat striatum

LIM homeodomain transcription factors play crucial roles in determining div erse aspects of neuronal development both in vertebrates and invertebrates. In the present study, we studied the expression pattern of Islet-1 (Isl-1) , a member of the LIM homeodomain protein family, in the rat striatum durin g development. The developmental expression of Isl-1 in the striatum is hig hly dynamic and complex in terms of spatial and temporal regulation. The re verse transcription-polymerase chain reaction and ribonuclease protection a ssays demonstrated that Isl-1 messenger RNA was expressed in the developing striatum. The immunocytochemical study of Isl-1 protein expression showed that there were prominent mediolateral and caudorostral Isl-1 gradients in the developing striatum. Numerous Isl-1-positive cells appeared in the medi al mantle zone of the developing striatal proper, and they co-expressed the postmitotic neuronal marker, microtubule-associated protein 2. The numbers of Isl-1-positive cells were decreased from the medial to the lateral regi ons, so that there were only a few Isl-1-positive cells scattered in the la teral striatum. These scattered Isl-1-positive cells were doubly labeled wi th tyrosine kinase receptor A and choline acetyltransferase, which indicate d that they were cholinergic neurons. The Isl-1 gradients were most promine nt in the embryonic day 18 and 20 striatum. With increases of time, the Isl -1 gradients were gradually reduced, and the gradients disappeared by postn atal day 7. Despite the general down-regulation of striatal Isl-1, a few Is l-1-positive cells were sustained into the adult striatum in which Isl-1 wa s nearly exclusively expressed by all cholinergic neurons and vice versa. O ur study suggests that Isl-1 is likely to be initially expressed by postmit otic cholinergic precursors and some, if not all, non-cholinergic precursor s in the developing striatum. During the progression of striatal differenti ation, Isl-1 is downregulated in non-cholinergic cells, but is sustained in cholinergic cells. The developmental restriction of Isl-1 to cholinergic n eurons in the striatum may represent a novel mechanism by which LIM homeodo main proteins specify specific cell types in the striatum during developmen t. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.