No abstract

Alzheimer's disease (AD) is a common, incurable, and progressive dementia, characterized by loss of learning and memory and the neuropathologic accumulation of amyloid plaques and neurofibrillary tangles in the brain. A number of similarities between AD pathology and several distinct retinal degenerations have been described, particularly with respect to either glaucoma or age-related macular degeneration (AMD), each a leading cause of vision loss and blindness worldwide. Although comparisons between these diseases may provide important new insights into their pathogenic mechanisms, glaucoma and AMD result in markedly different degenerations. Therefore, analyses of the differences and the similarities between these conditions may prove equally productive. Common mechanisms that appear to underlie all three diseases are explored here, as well as potential use of the retina as a biomarker for AD diagnosis and progression. Based on this comparison, past and current efforts to transfer therapeutic strategies between diseases are discussed.

Vertebrate gastrulation requires coordination of mesoderm specification with morphogenetic movements. While both of these processes require FGF signaling, it is not known how mesoderm specification and cell movements are coordinated during gastrulation. The related Sprouty and Spred protein families are recently discovered regulators of receptor tyrosine kinase signaling. We identified two genes for each family in Xenopus tropicalis: Xtsprouty1, Xtsprouty2, Xtspred1, and Xtspred2. In gain- and loss-of-function experiments we show that XtSprouty and XtSpred proteins modulate different signaling pathways downstream of the FGF receptor (FGFR), and consequently different developmental processes. Notably, XtSproutys inhibit morphogenesis and Ca(2+) and PKCdelta signaling, leaving MAPK activation and mesoderm specification intact. In contrast, XtSpreds inhibit MAPK activation and mesoderm specification, with little effect on Ca(2+) or PKCdelta signaling. These differences, combined with the timing of their developmental expression, suggest a mechanism to switch FGFR signal interpretation to coordinate mesoderm formation and cell movements during gastrulation.