Islet-1 (ISL1 transcription factor, LIM/homeodomain) and Islet-2 (ISL2 transcription factor, LIM/homeodomain) contain amino-terminal LIM domains and a carboxy-terminal homeodomain and both influence developmental events. Islet-1 influences embryogenesis of the pancreatic islets of Langerhans and neural tube motor neuron differentiation. In developing mouse teeth, Islet-1 mediates patterning of dentition as an activator of Bmp4 expression in incisor (distal) areas of the stomatodeal epithelium. Islet-1 expression defines cardiac progenitor cell populations and is required for normal cardiac development and asymmetry. Islet-2 activity in newly generated motor neurons permits the diversification of visceral and somatic motor neuron subtypes in the developing spinal cord. Murine Islet-2 specifies retinal ganglion cell (RGC) laterality by repressing an ipsilateral pathfinding program unique to the ventral-temporal crescent (VTC) of RGCs in a Zic2- and EphB1-dependent manner.