During this process, EphB or ephrinBs are required for RGCs to dictate their final position in the superior colliculus (Hindges et al

During this process, EphB or ephrinBs are required for RGCs to dictate their final position in the superior colliculus (Hindges et al., 2002; Thakar et al., 2011). data 3: RGC loss is dependent on Dcc signaling. elife-51275-fig7-data3.xlsx (12K) GUID:?52B9BA85-BC42-4C68-BA6D-9958BF052E83 Figure 8source data 1: Rosette volume in cKO mice does not progress overtime. elife-51275-fig8-data1.xlsx (41K) GUID:?F4E44AE4-1373-4ABF-AAD3-57B2D825500E Figure 8source data 2: Rabbit Polyclonal to OR2T2/35 EyeDISCO leads to MIR96-IN-1 a mild and isotropic shrinkage of the adult mouse eye. elife-51275-fig8-data2.xlsx (43K) GUID:?2DFB83A7-D2FD-42A6-950C-E44625E41B6F Figure 8source data 3: Outer nuclear layer thickness is reduced in Dcc cKo mice. elife-51275-fig8-data3.xlsx (48K) GUID:?1676CBB8-07B9-4749-9C96-7B5A238EED00 Figure 8source data 4: Retinal-specific deletion of Dcc leads to a significant reduction in retinal physiology. elife-51275-fig8-data4.xlsx (240K) GUID:?79A8B537-F13B-4AE0-921D-B0473E20D501 Supplementary file 1: List of primary and secondary antibodies used for the study. elife-51275-supp1.docx (17K) GUID:?40CF65C6-A86A-4685-9F5C-09EBF13DD725 Supplementary file 2: List of primary antibodies validated with the EyeDISCO clearing protocol. elife-51275-supp2.xlsx (27K) GUID:?795FCC7C-D85A-4787-AC0F-C2E0B9BA15D2 Supplementary file 3: Sequencing of Phosphodiesterase 6b, cGMP, rod receptor, beta polypeptide (Pde6b) mutations in the cKO and mice. elife-51275-supp3.docx (61K) GUID:?6031D44F-ACA2-4DC3-950B-4C857345DEAD Supplementary file 4: Key resources table. elife-51275-supp4.docx (40K) GUID:?43A3C7A1-A77E-4B88-86CF-1EA75E4C4742 Transparent reporting form. elife-51275-transrepform.docx (250K) GUID:?C70BFBDD-0A88-4178-8592-517F9C9F8333 Data Availability StatementAll data generated or analysed during this study are included in the manuscript and supporting files. All source files are provided. Abstract The Deleted in Colorectal Carcinoma (Dcc) receptor plays a critical role in optic nerve development. Whilst Dcc is expressed postnatally in the eye, its function remains unknown as knockouts die at birth. To circumvent this drawback, we generated an eye-specific mutant. To study the organization of the MIR96-IN-1 retina and visual projections in these mice, we also established EyeDISCO, a novel tissue clearing protocol that removes melanin allowing 3D imaging of whole eyes and visual pathways. We show that in the absence of were also identified in patients suffering from rare neurodevelopmental disorders including congenital mirror movements (Depienne et al., 2011; Srour et al., 2010) and corpus callosum dysgenesis (Jamuar et al., 2017; Marsh et al., 2017). Dcc is present in the developing central nervous system (CNS) and controls axon guidance and cell migration in the spinal cord, as well as in multiple brain areas (Belle et al., 2014; Fazeli et al., 1997; Fothergill et al., MIR96-IN-1 2014; Laumonnerie et al., 2014; Schmidt et al., 2014; Srivatsa et al., 2014; Yee et al., 1999). Dcc expression persists in the postnatal and adult CNS where it is involved in synaptogenesis (Horn et al., 2013; Manitt et al., 2013) and myelination (Jarjour et al., 2008). In vivo evidence supporting Dcc function in CNS development was primarily obtained using knockout (KO) mice (a null allele) which lack Dcc in all cells (Fazeli et al., 1997). One of the most striking phenotype, a hypoplasia of the optic nerve, was reported in the visual system (Deiner et al., 1997; Shi et al., 2010). In KO embryos, a large fraction of the retinal ganglion cell (RGC) axons which connects the eye to the brain via the optic nerve is unable MIR96-IN-1 to exit the retina (Deiner et al., 1997). The presence of its ligand Netrin-1 at the optic disc, the exit point of the retina, together with the presence of hypoplasic optic nerves in hypomorph mutant embryos suggested that Netrin-1 acts as a long range cue attracting Dcc-expressing RGC axons towards the optic nerve head MIR96-IN-1 (Deiner et al., 1997; Shi et al., 2010). Dcc expression persists in RGC axons after they exit the retina and even postnatally (Shi et al., 2010) but as null mice die at birth (Fazeli et al., 1997), its function at later stages of visual system development is unknown. In tadpoles, Netrin-1 attracts RGC axons toward the optic disc (Shewan et al., 2002) and promotes RGC axon arborization and synapse formation within the tectum (Manitt et al., 2009). Importantly, recent studies using conditional knockout strategies have revisited the role of Netrin-1 in axon guidance at the CNS midline and suggested that Netrin-1 does not act as a long-range attractive cue for axons (Dominici et al., 2017; Moreno-Bravo et al., 2019; Varadarajan et al., 2017; Wu et al., 2019). Although the conditional ablation of in specific neuronal classes recapitulates the axon guidance.