Nr2e1 is expressed predominantly in the forebrain and dorsal midbrain regions throughout development^[1] and remains expressed in the adult subventricular and subgranular zones, areas of active neurogenesis^[2][3][4]. Expression begins as early as E8 in the brain and peaks at E12.5^[1], after which expression drops until after birth^[5]. At E12.5, expression is high in the lateral telencephalon (dorsal and lateral pallium, and lateral ganglionic eminence), and low in the dorsomedial pallium and medial ganglionic eminence^[6]. In the eye, Nr2e1 is expressed in the neural retina and optic stalk at E13^[7]. Specifically, Nr2e1 is expressed in retinal progenitor cells, Müller glia, and astrocytes^[8], including proangiogenic retinal astrocytes^[9]. At E14.5, expression is similar to E12.5 but also in the ventricular zone of the third ventricle^[6]. Expression is also observed in the adult retina and is required for vision^{[10][11][7][12][13]}. Nr2e1 is expressed in neural stem cells and co-stains with nestin, RC2, and almost always with BrdU and Ki67^{[14][15][16][17][18]}. Nestin co-expression in the SVZ and SGZ was verified with a β-galactosidase reporter knocked-in at the Nr2e1 locus^[14]. Sparse expression was also observed in the cortex^[14]. When isolated using FACS, β-gal-positive presumptive NSCs isolated from brain tissue proliferate in NSC-proliferation medium^[14].

In vivo, expression is limited to type B neural stem cells (co-stained with Gfap), and not in type C transitly-amplifying progenitors or type A immature migratory neuroblasts^[2]. Nr2e1 is also required for the transition from radial glial to astrocyte-like NSCs around P9^[16]. Interestingly, a sub-population of excitatory glutamatergic neurons express Nr2e1 as well, where its function is unknown^[3].

An Nr2e1 BAC driving cre recombinase crossed to a ROSA26 mouse indicated that expression is found in the subventricular zone, rostral migratory stream, and dentate gyrus of the hippocampus^[2]. This expression is confirmed by Allen Brain Atlas in situ hybridization.

In Drosophila, tailless (Nr2e1) does not seem to be self-regulatory^[19], consistent with studies of β-gal expression in Nr2e1^lacZ/- mice^[14].

In Xenopus, Xtll (Nr2e1) expression has been detected in the brain, eye, and testes^[10]; however, in mouse, Nr2e1 was not detected in testes^[20]. In Fugu, expression is strongly observed in the brain and eye^[11].

In vitro, Nr2e1 is detected under proliferation and not differentiation conditions of neural stem cells, wherein it is localized to the nucleus^[15]. The regulation of NSC proliferation is primarily in a cell-autonomous fashion, as growth factors from surrounding wild-type cells cannot rescue the proliferation defects of null cells^[3].

In the eye, Nr2e1 expression is rapidly downregulated upon contact with blood vessels and levels are regulated by oxygen concentration^[9]. Co-expression of VEGF and fibronectin is found in retinal astrocytes, where Nr2e1 is important for establishing the retinal astrocyte extracellular fibronectin network^[9].