Conserved roles of ems/Emx and otd/Otx genes in olfactory and visual system development in Drosophila and mouse

Abstract

The regional specialization of brain function has been well documented in the mouse and fruitfly. The expression of regulatory factors in specific regions of the brain during development suggests that they function to establish or maintain this specialization. Here, we focus on two such factors-the Drosophila cephalic gap genes empty spiracles (ems) and orthodenticle (otd), and their vertebrate homologues Emx1/2 and Otx1/2-and review novel insight into their multiple crucial roles in the formation of complex sensory systems. While the early requirement of these genes in specification of the neuroectoderm has been discussed previously, here we consider more recent studies that elucidate the later functions of these genes in sensory system formation in vertebrates and invertebrates. These new studies show that the ems and Emx genes in both flies and mice are essential for the development of the peripheral and central neurons of their respective olfactory systems. Moreover, they demonstrate that the otd and Otx genes in both flies and mice are essential for the development of the peripheral and central neurons of their respective visual systems. Based on these recent experimental findings, we discuss the possibility that the olfactory and visual systems of flies and mice share a common evolutionary origin, in that the conserved visual and olfactory circuit elements derive from conserved domains of otd/Otx and ems/Emx action in the urbilaterian ancestor.

Keywords: Emx1/2, Otx1/2; empty spiracles; evolutionary conservation; orthodenticle; sensory systems.

Figure 1.

ems/Emx genes control the development of the olfactory system in flies and mice. (a) The origins of the olfactory neurons in Drosophila larvae and adults can be traced back to the Ems-expressing antennal head segment (green stripe in the anterior of the embryo). The larval dorsal organ originates in this segment (green arrow on the left). The neuroblasts that give rise to the deutocerebral larval antennal lobe (grey dotted lines in the brain) and the deutocerebral adult antennal lobe (dark grey shaded area in the brain) delaminate from this Ems-expressing antennal head segment (middle green arrow). The eye–antennal disc (EAD), the antennal part of which gives rise to the adult antenna, also incorporates into it cells from the Ems-expressing antennal head segment (green arrow on the right). (b) The WT larval PNs innervating the larval antennal lobe and restricting their dendrites to the confines of the larval antennal lobe (white dotted line). (c) The WT OR-45a expressing OSN with terminals confined to a single glomerulus in the antennal lobe (white dotted line). (d) The PNs are null for ems function and have innervations leaving the antennal lobe (magenta arrows; compare with PNs in (b)). (e) The OR-45a expressing OSN are null for ems function and they have targeting defects (magenta arrow; compare with OSN in (c)). (f,h) Compare the similarity in the olfactory circuits of flies and mice—OSNs (blue neurons) target glomeruli (coloured circles) in the antennal lobe (AL)/olfactory bulb (OB), glomerular specific PNs/mitral–tufted cells (green neurons) take olfactory information to higher brain centres and LNs/periglomerular cells (pink neurons) perform local information processing between glomeruli. (g,i) Summary of the mutant phenotypes observed in the OSNs, PNs and LNs in flies and mice, respectively, when these neurons/structures are null for ems/Emx function. ems null fly OSNs fail to respect glomerular and antennal lobe boundaries (blue arrowheads; compare blue neurons in (f,g)). ems null fly PNs from one neuroblast also fail to respect glomerular and antennal lobe boundaries (green arrowheads; compare green neurons in (f,g)). ems null fly LNs and PNs from another neuroblast undergo apoptosis (compare pink neurons in (f,g)). Emx null mice have disrupted nasal epithelia and fewer OSNs, which are unable to target the olfactory bulb (compare blue arrowheads and neurons in (h,i); also compare nasal epithelium in (h,i)). The mitral–tufted cells (green neurons) and the periglomerular cells (pink neurons) also fail to target the glomerular layer (compare green and pink arrowheads in (h,i)), which is also disrupted (compare glomerular layers in (h,i)).

Figure 2.

otd/Otx genes control the development of the visual system in flies and mice. (a) The origins of the visual neurons in Drosophila larvae and adults can be traced back to the Otd-expressing ocular head segment (red stripe in the anterior of the embryo). The larval Bolwig's organ originates in this segment (red arrow on left). The optic lobe of the larva and the adult also originate in this segment (middle red arrow). The eye–antennal disc, which gives rise to the adult eye, also incorporates into it cells from the Otd-expressing domain (red arrow on right). (b) The similarity in the visual circuits of flies and mice. Photoreceptor cells in both flies and mice (green neurons) project in parallel to a number of interneuronal types (pink and blue neurons). The interneurons are arranged in multiple parallel cell layers (grey structures) that are interconnected orthogonally. (c) The mutant phenotypes observed in photoreceptor neurons in otd null flies and Crx null mice. Note that in both cases, the rhabdomere/outer segment of the PR neurons fails to develop (compare WT and otd^−/− PRs in flies, and WT and Crx^−/− PRs in mice). Also summarized is the phenotype seen in the eyes of mice null for Otx function. Note the change in orientation of eye structures and also the expansion of the neural retina at the expense of the retinal pigment epithelium in the Otx null mice. EAD, eye–antennal disc; PR, photoreceptor; LGN, lateral geniculate nucleus; RPE, retinal pigment epithelia; NR, neural retina; OS, outer segment.