The highly ordered assembly of retinal axons and their synaptic partners is regulated by Hedgehog/Single-minded in theDrosophilavisual system

Abstract

During development of the Drosophila visual center, photoreceptor cells extend their axons (R axons) to the lamina ganglion layer, and trigger proliferation and differentiation of synaptic partners (lamina neurons) by delivering the inductive signal Hedgehog (Hh). This inductive mechanism helps to establish an orderly arrangement of connections between the R axons and lamina neurons, termed a retinotopic map because it results in positioning the lamina neurons in close vicinity to the corresponding R axons. We found that the bHLH-PAS transcription factor Single-minded (Sim) is induced by Hh in the lamina neurons and is required for the association of lamina neurons with R axons. In sim mutant brains, lamina neurons undergo the first step of differentiation but fail to associate with R axons. As a result, lamina neurons are set aside from R axons. The data reveal a novel mechanism for regulation of the interaction between axons and neuronal cell bodies that establishes precise neuronal networks.

A conserved transcriptional network regulates lamina development in the Drosophila visual system

“…Differentiating lamina cells expressing sim are located posterior to the LF (Umetsu et al, 2006). Expression of sim is detected weakly and uniformly in the preassembly domain, but clear nuclear staining can be seen only in the assembly domain (Umetsu et al, 2006) (Fig. 1C,D).…”

“…The differentiation of lamina neurons is triggered by Hh. Differentiation progresses as a fan-shaped wave marked by an indentation, the LF (Selleck and Steller, 1991), which moves from lateral to medial as incoming axons are sent in by newly formed rows of ommatidia (Umetsu et al, 2006). This is reminiscent of the Hh-driven movement of the morphogenetic furrow in the eye (Wolff and Ready, 1991).…”

“…1E,G). The onset of dac expression starts posterior to the LF, in its posterior slope, and is maintained throughout lamina development (Huang and Kunes, 1996;Chotard et al, 2005;Umetsu et al, 2006). Differentiating lamina cells expressing sim are located posterior to the LF (Umetsu et al, 2006).…”

“…Lamina cells are characterized by the expression of the transcription factor dachshund (dac) (Mardon et al, 1994;Huang and Kunes, 1996). As cells exit the LF, they are contacted by incoming retinal PR axons in what is termed the preassembly domain (Umetsu et al, 2006). Hedgehog (Hh), delivered by PR axons, triggers the lamina differentiation program along with a final cell division (Selleck and Steller, 1991;Huang and Kunes, 1996;Huang et al, 1998).…”

“…Hedgehog (Hh), delivered by PR axons, triggers the lamina differentiation program along with a final cell division (Selleck and Steller, 1991;Huang and Kunes, 1996;Huang et al, 1998). Next, lamina cells and PR axons reorganize and assemble into lamina columns (Meinertzhagen and Hanson, 1993), a process that requires the expression of the bHLH-PAS transcription factor single-minded (sim) (Umetsu et al, 2006).…”