The optic lobe forms a prominent compartment of the Drosophila adult brain that processes visual input from the compound eye. Neurons of the optic lobe are produced during the larval period from two neuroepithelial layers called the outer and inner optic anlage (OOA, IOA). In the early larva, the optic anlagen grow as epithelia by symmetric cell division. Subsequently, neuroepithelial cells (NE) convert into neuroblasts (NB) in a tightly regulated spatio-temporal progression that starts at the edges of the epithelia and gradually move towards its centers. Neuroblasts divide at a much faster pace in an asymmetric mode, producing lineages of neurons that populate the different parts of the optic lobe. In this paper we have reconstructed the complex morphogenesis of the optic lobe during the larval period, and established a role for the Notch and Jak/Stat signaling pathways during the NE-NB conversion. After an early phase of complete overlap in the OOA, signaling activities sort out such that Jak/Stat is active in the lateral OOA which gives rise to the lamina, and Notch remains in the medial cells that form the medulla. During the third instar, a wave front of enhanced Notch activity progressing over the OOA from medial to lateral controls the gradual NE-NB conversion. Neuroepithelial cells at the medial edge of the OOA, shortly prior to becoming neuroblasts, express high levels of Delta, which activates the Notch pathway and thereby maintains the OOA in an epithelial state. Loss of Notch signaling, as well as Jak/Stat signaling, results in a premature NE-NB conversion of the OOA, which in turn has severe effects on optic lobe patterning. Our findings present the Drosophila optic lobe as a useful model to analyze the key signaling mechanisms controlling transitions of progenitor cells from symmetric (growth) to asymmetric (differentiative) divisions.

[reaction: see text] A phosphine-catalyzed reaction of an allenoate with aldehydes furnished (2,6-diaryl-[1,3]dioxan-4-ylidene)-acetates 4 in excellent to moderate yields with complete diastereoselectivity and high E/Z-selectivities. Upon removal of the acetal functionality in this domino reaction product 4, delta-hydroxy-beta-ketoester 11 was obtained. The reported vinylphosphonium-based approach provides a new way to achieve a synthesis of delta-hydroxy-beta-ketoesters that differs from the classical dianion-based approach.

Purpose: Epiretinal proliferation is a distinct clinical entity from epiretinal membrane that is classically associated with lamellar macular holes, but its prevalence and association with full-thickness macular holes (FTMH) have not been well described. We characterize MHEP macular hole associated epiretinal proliferation (MHEP) and its effects on long-term surgical outcomes. Design: Multi-center, interventional, retrospective case control study. Subjects: Consecutive eyes that underwent surgery for FTMH with a minimum of 12-months follow-up. Methods: All eyes underwent pars plana vitrectomy, removal of any epiretinal membranes, and gas tamponade, with or without internal limiting membrane peeling. Spectral domain optical coherence tomography imaging was obtained pre- and post-operatively. Main Outcome Measures: Improvement in visual acuity and single surgery hole closure rates in eyes with, versus without, MHEP at 12 months. Results: 725 charts were analyzed, and 113 patients met inclusion criteria. Of 113 eyes with FTMH, 30 (26.5%) had MHEP. Patients with FTMH and MHEP were older (P < 0.002), more often male (P = 0.001), and with more advanced macular hole stages than those without MHEP (P = 0.010). A full posterior vitreous detachment was more common in eyes with MHEP (P < 0.004). FTMH with MHEP had significantly less improvement in visual acuity 12-months postoperatively (P = 0.019) with higher rates of ellipsoid and external limiting membrane defects (P < 0.05) and with a higher rate of failure to close with one surgery compared to FTMH without MHEP (26.7% versus 4.8% [P = 0.002]). Peeling the internal limiting membrane was associated with improved rates of hole closure in FTMH with MHEP (P < 0.001). Multivariable testing confirmed that the presence of MHEP was an independent risk factor for less visual improvement (P = 0.031), single-surgery non-closure (P = 0.009), and that ILM peeling improved single-surgery closure rates (P = 0.026). Conclusions: We found that FTMH with MHEP has poorer anatomic and visual outcomes after vitrectomy compared to FTMH without MHEP. ILM peeling was associated with improved closure rates and should be considered when MHEP is detected preoperatively.

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