We report successful retinal cone enrichment and transplantation using a novel cone-GFP reporter mouse line. Using the putative cone photoreceptor-enriched transcript Coiled-Coil Domain Containing 136 (Ccdc136) GFP-trapped allele, we monitored developmental reporter expression, facilitated the enrichment of cones, and evaluated transplanted GFP-labeled cones in wildtype and retinal degeneration mutant retinas. GFP reporter and endogenous Ccdc136 transcripts exhibit overlapping temporal and spatial expression patterns, both initiated in cone precursors of the embryonic retina and persisting to the adult stage in S and S/M opsin+ cones as well as rod bipolar cells. The trapped allele does not affect cone function or survival in the adult mutant retina. When comparing the integration of GFP+ embryonic cones and postnatal Nrl−/− ‘cods’ into retinas of adult wildtype and blind mice, both cell types integrated and exhibited a degree of morphological maturation that was dependent on donor age. These results demonstrate the amenability of the adult retina to cone transplantation using a novel transgenic resource that can advance therapeutic cone transplantation in models of age-related macular degeneration.
Humans are exposed to potentially harmful agents (bacteria, viruses, toxins) throughout our lifespan; the consequences of such exposure can alter central nervous system development. Exposure to immunogens during pregnancy increases the risk of developing neurological disorders such as schizophrenia and autism. Further, sex hormones, such as estrogen, have strong modulatory effects on immune function and have also been implicated in the development of neuropathologies (e.g., schizophrenia and depression). Similarly, animal studies have demonstrated that immunogen exposure in utero or during the neonatal period, at a time when the brain is undergoing maturation, can induce changes in learning and memory, as well as dopaminemediated behaviors in a sex-specific manner. Literature that covers the effects of immunogens on innate immune activation and ultimately the development of the adult brain and behavior is riddled with contradictory findings, and the addition of sex as a factor only adds to the complexity. This review provides evidence that innate immune activation during critical periods of development may have effects on the adult brain in a sex-specific manner. Issues regarding sex bias in research as well as variability in animal models of immune function are discussed.
Despite the apparent uniformity in cellular composition of the adult mammalian cerebellar cortex, it is actually highly compartmentalized into transverse zones and within each zone further subdivided into a reproducible array of parasagittal stripes. This basic cerebellar architecture is highly conserved in birds and mammals. However, different species have very different cerebellar morphologies, and it is unclear if cerebellar architecture reflects taxonomic relations or ecological niches. To explore this, we have examined the cerebellum of the naked mole-rat Heterocephalus glaber, a burrowing rodent with adaptations to a subterranean life that include only a rudimentary visual system. The cerebellum of H. glaber resembles that of other rodents with the remarkable exception that cerebellar regions that are prominent in the handling of visual information (the central zone, nodular zone, and dorsal paraflocculus) are greatly reduced or absent. In addition, there is a notable increase in size in the posterior zone, consistent with an expanded role for the trigeminal somatosensory system. These data suggest that cerebellar architecture may be substantially modified to serve a particular ecological niche.
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