Transcription factor involved in SHH-dependent neural patterning (PubMed:10830170, PubMed:15201216). Together with NKX2-2 and NKX6-1 acts to restrict the generation of motor neurons to the appropriate region of the neural tube (PubMed:10830170, PubMed:15201216). Belongs to the class I proteins of neuronal progenitor factors, which are repressed by SHH signals (PubMed:10830170, PubMed:15201216). Involved in the transcriptional repression of MNX1 in non-motor neuron cells (PubMed:15201216). Acts as a regulator of energy metabolism (PubMed:24646999). Expressed by neural progenitor cells in discrete domains of the ventral neural tube. Also expressed in specific and overlapping patterns with Irx1 and Irx2 in the developing and adult metanephric kidney. In the adult metanephros, renal expression is confined to the S3 segment of the proximal tubule, in the loop of Henle. The earliest expressed of the Irx family, with expression seen in trophectoderm-derived extraembryonic tissues from 6.5 dpc, including expression in the chorionic ectoderm at 8.0 dpc. Embryonic expression starts at the end of gastrulation (7.5 dpc) in the ectodermal layer which gives rise to the nervous system. At 8.0 dpc, expression is confined to the thickening neural ectoderm corresponding to the future mesencephalon (midbrain) and rhombencephalon (hindbrain) and from 8.5 dpc onwards, expression also includes the rostral part of the closing neural tube. After neural tube closure at 9.5 dpc, expression predominates in the CNS in the midbrain, hindbrain and spinal cord. Also expressed in a number of tissues outside of the CNS including ectodermal layer of the branchial arches. Expressed in the prospective limb buds of the lateral plate mesoderm, and from 10.5 dpc onwards a gradient exists along the dorsoventral and proximodistal axes of developing limbs. Expressed in the notochord at stage 9.0 dpc. At 9.5 dpc found in the cephalic mesoderm surrounding the optic vesicle. Around 10.5 dpc, expression in the head mesoderm extends into the nasal pits. By 12.5 dpc, still expressed in the mesenchyme, and expressions begins in specific subsets of post-mitotic cells in the neuroretina. As development ensues, expression increases in the neuroretina and mesenchymal expression gradually decreases. At 16.5 dpc, expressed exclusively in the inner neuroblast layers of the neuroretina. In the developing heart, first expressed in the trabecules of embryonic ventricles at 9.5 dpc, and from then onwards localizes specifically to the trabeculated myocardium of the ventricles. Mice are viable and fertile but display a significant reduction of body weight, primarily through the loss of fat mass and increase in basal metabolic rate with browning of white adipose tissue. Belongs to the TALE/IRO homeobox family.