Isl1, the insulin enhancer-binding protein islet-1, is a LIM-homeodomain transcription factor. It plays a key role in multiple organs during embryonic development, especially in cardiovascular development where it serves as a marker gene for the second heart field progenitors [1]. Isl1 also participates in pathways like Shh signaling and is involved in histone H3 lysine 4 (H3K4) methylation through its association with Set1/Mll complexes, thus influencing gene transcription [2,3].

In various KO/CKO mouse models, Isl1 has been shown to have diverse functions. Ablation of Isl1 in lung epithelium led to defective lung branching morphogenesis due to down-regulation of genes in the Shh signaling pathway [2]. Deletion in the mouse mandibular epithelium caused aglossia as Isl1 regulates myoblast migration through the Shh/Wnt5a/Cxcl12 cascade [4]. Selective knockout in auditory neurons disrupted the formation of the spiral ganglion, cochlear wiring, and tonotopic organization [5]. In pancreatic studies, elimination of Isl1 resulted in a diabetic phenotype with loss of α cells and disrupted β cell maturation [6].

In conclusion, Isl1 is essential for multiple developmental processes including lung, tongue, auditory neuron, and pancreatic cell development. The use of Isl1 KO/CKO mouse models has revealed its significance in disease-related phenotypes such as diabetes. Understanding Isl1's functions provides insights into the molecular basis of these biological processes and potential disease mechanisms.