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Homo sapiens
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Mus musculus
Homo sapiens
Mus musculus
Transcription Factor Encyclopedia  BETA
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Islet-1 (Isl1) is a LIM-Homeodomain transcription factor, initially identified as an insulin gene enhancer binding protein [1]. Isl1 gene is evolutionary conserved and it contains six exons and is located in chromosome 13 in mouse and chromosome 5 in human. Isl1 regulates gene expression by binding of its homeodomain to AT-rich sequences containing a core TAAT motifs. One alternatively spliced variant of Isl1 has been identified from mouse beta-cell, but functional consequence of this alternative splicing is not clear [2]. Another member of Islet family is Isl2 (chr15 in human and chr9 in mouse), which shares high homology with Isl1. Isl1 and Isl2 display an overlapping expression pattern, with Isl2 being more restricted, and play largely redundant role [3][4]. Isl1 exhibits a distinct expression pattern during development in multiple cell types, including neurons of basal ganglia [5], spinal motor neurons [4][6][7], retina, peripheral nervous system, pancreas [1][8][9][10], pharyngeal/ foregut endoderm and cardiogenic mesoderm [11][12][13][14]. Recent genetic studies have revealed essential roles of Isl1 in cell specification, differentiation and survival. Isl1 is also required for the pancreatic development [8]. Isl1 is required for development of a subset of forebrain cholinergic neurons, and retinal ganglion cells, and retinal Bipolar and cholinergic amacrine cells [15][16][17]. Combinatory expression of LIM domain transcription factors, including Isl1, Lim3, Lmo4 and NLI/Ldb1, which form highly ordered complexes, referred as to LIM codes, play essential roles in specification of spinal motor neuron versus V2 interneuron [4][18][19][20]. In sensory neurons of the DRG and trigeminal ganglia, Isl1 plays essential roles in coordination of sensory neuronal gene program that ensure neuronal survival and differentiation [21]. Isl1 marks the cardiogenetic progenitors of the second heart field and is required for proliferation, differentiation, migration and survival of these progenitors [11][22]. Isl1 appears to play a central role in the cardiac genetic programs that regulate cardiac morphogenesis and function. Isl1 is downstream of Wnt/-catenin and FGF8 signaling but upstream of BMP4, BMP7, FGF10, Shh and Foxh1 [23][24][25][26][27][28]. Isl1 is a direct downstream target of Forkhead transcription factors [29]. Mef2c is a direct downstream target of Isl1. Binding of Isl1 and GATA4 to their respective binding site in Mef2c cardiac enhancer is required for cardiac expression of this enhancer [30]. A GATA4 and Isl1 binding sites have been found in a cardiac enhancer upstream of Nkx2.5 gene and expression of this enhance in cardiac region is dependent on GATA4 and Isl1 [31][32]. In addition, Isl1 is known to bind its preferred consensus element YTAATGR and regulate the promoters of the insulin, glucagon and somatostatin genes [1][33][34][35]. Interestingly, a heterozygous nonsense mutation in isl1 gene was found in one patient with type 2 diabetes [36]. Given its distinct expression pattern and important roles during development, it is tempting to speculate that Isl1 may be involved in human congenital diseases, including congenital heart diseases.

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  12. Park EJ et al. An FGF autocrine loop initiated in second heart field mesoderm regulates morphogenesis at the arterial pole of the heart. Development, 135(21):3599-610. (PMID 18832392)
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FIGURE 1 Expression of Isl1 in Mouse Embryo and Role of Isl1 in Cardiac Genetic Networks
A. Isl1 exhibits a distinct expression pattern during development in multiple cell types, including neurons in the central and peripheral nervous systems and cardiogenic region. B. Isl1 play an central role in genetic networks that regulate cardiac development and function.
This figure was created by the authors of this article. The authors of this article have provided the assurance that this figure constitutes their original work.