Retinogenesis in vertebrates is stereotyped in an ordered fashion: retinal ganglion cells are always born first, followed by horizontal, amacrine, and cone cells, and finally by bipolar, rod, and M��ller cells [1, 2]. During retinal cell type development, transcription factors play critical roles in the generation of diverse neuronal phenotypes, and Nutlin-3a price genetic manipulation of these molecules often leads to an alteration of one or more retinal cell phenotypes [3�C6]. The LIM-homeodomain transcription factor Islet-1 (Isl1) orchestrates cell fate decisions in a variety of systems [7, 8]. Different studies have shown that, in the retina, Isl1 is expressed in mature and differentiating ganglion, amacrine, bipolar, and horizontal cells, suggesting that it plays a pivotal role in the maturation of these cell types in fish [9�C11], reptiles [12], birds [13�C21], and mammals [22�C28].

In particular, Isl1 expression has been demonstrated to be required for neuronal progenitors to specify retinal ganglion cell fate in mammals, activating genes essential for cell differentiation [25, 26, 28]. In addition, it participates in the regulation of the development of cholinergic amacrine cells in mammals [22�C24] and birds [29]. It also controls the differentiation of bipolar cells in mammals [22, 23]. Furthermore, Isl1 is involved in horizontal cell determination [16, 20] and regulates the morphogenesis of subsets of postmigratory horizontal cells in the chick [19]. Surprisingly, although Isl1 is not normally expressed by horizontal cells in the developing and mature mouse retina [22�C24], it participates in determining horizontal cell number [30].

There have been few reports describing Isl1 expression during amphibian central nervous system development. The South African clawed frog Xenopus laevis (Daudin, 1802) is a suitable model to study different aspects of central nervous system development, and, recently, implications of Isl1 in diverse aspects of regional development and neuronal specification in the forebrain have been demonstrated [31]. Furthermore, several authors have used Isl1 as an early marker of ganglion cells during development in this anuran species [32�C34], but the detailed spatiotemporal expression of this transcription factor during retinal development has not previously been described.

The aim of our study was to analyze immunohistochemically the onset and the dynamic expression of Isl1 during retinal development of X. laevis. The structural arrangement of the retina was examined in toluidine blue-stained resin sections and in cryosections labeled with Batimastat DAPI. We characterized the subpopulations of Isl1-expressing cells by both morphological and topographical features, but also by double immunolabeling with other retinal markers, whose distribution we have previously studied in the developing and mature retina of different vertebrates [9�C12, 35, 36].