Tissue organization in Drosophila is regulated by the core planar cell polarity (PCP) proteins Frizzled, Dishevelled, Prickle, Van Gogh and Flamingo. Core PCP proteins are conserved in mammals and function in mammalian tissue organization. Recent studies have identified another group of Drosophila PCP proteins, consisting of the protocadherins Fat and Dachsous (Ds) and the transmembrane protein Four-jointed (Fj). In Drosophila, Fat represses fj transcription, and Ds represses Fat activity in PCP. Here we show that Fat4 is an essential gene that has a key role in vertebrate PCP. Loss of Fat4 disrupts oriented cell divisions and tubule elongation during kidney development, leading to cystic kidney disease. Fat4 genetically interacts with the PCP genes Vangl2 and Fjx1 in cyst formation. In addition, Fat4 represses Fjx1 expression, indicating that Fat signaling is conserved. Together, these data suggest that Fat4 regulates vertebrate PCP and that loss of PCP signaling may underlie some cystic diseases in humans.

Our study concerns the mechanisms that underlie functional imaging of sensory areas of cortex using hemodynamic-based methods such as optical imaging of intrinsic signals, functional magnetic resonance imaging and positron emission tomography. In temporal cortex of chinchilla, we have used optical imaging of intrinsic signals evoked by acoustic stimulation to define the functionally responsive area and then made (scanning electron microscopy) observations of the corresponding capillary networks prepared by corrosion cast methods. We report that intrinsic signals associated with auditory cortex correlate directly with discrete capillary beds. These capillary beds, within the cortical surface layers, are distributed across the cortex in a non-uniform fashion. Within cortex both the arterial supply and the capillary network contain various flow control structures. Our study suggests a causal relationship between the metabolic demands of local neuronal activity and both the density of the capillary network and the placement of the control structures. Such relationships will affect the ultimate spatial resolution obtainable by hemodynamic-based functional brain imaging studies. These relationships will also affect quantitative comparisons of activity levels in different areas of cortex.

A range of basic and applied studies have demonstrated that during the development of the auditory system, early experimental manipulations or clinical interventions are generally more effective than those made later. We present a short review of these studies. We investigated this age-related plasticity in relation to the timing of cochlear implantation in deaf-from-birth children. Cochlear implantation is a standard intervention for providing hearing in children with severe to profound deafness. An important practical question is whether there is a critical period or cutoff age of implantation after which hearing outcomes are significantly reduced. In this article, we present data from prelingually deaf children (mostly congenitally deaf) implanted at ages ranging from 1 to 15 years. Each child was tested with auditory and speech understanding tests before implantation, and at regular intervals up to 8 years postimplantation. We measured the improvement in performance of speech understanding tests in younger implanted children and compared it with the results of those implanted at a later age. We also used a binary partitioning algorithm to divide the data systematically at all ages at implant to determine the optimum split, i.e., to determine the age at implant which best separates performance of early implanted versus later implanted children. We observed distinct age-of-implant cutoffs, and will discuss whether these really represent critical periods during development.

Background and Purpose-Hereditary hemorrhagic telangiectasia type 1 (HHT1) is an autosomal dominant vascular dysplasia caused by mutations in the endoglin gene and characterized by dilated vessels and arteriovenous malformations (AVMs). To understand the etiology of this disorder, we evaluated the cerebral vasculature of endoglin heterozygous (Eng ϩ/Ϫ ) mice, which represent the only animal model of HHT1. Methods-The cerebral vasculature of Eng ϩ/Ϫ and Eng ϩ/ϩ mice from C57BL/6 (B6) and 129/Ola (129) strains with a differential susceptibility to HHT1 was studied with corrosion casting. Casts were observed by scanning electron microscopy to detect malformations and evaluate arterial diameters and orientation of endothelial nuclei. Measurements were taken to assess relative constriction at arteriolar branching points and downstream relative dilatation. Results-Three of 10 Engϩ/Ϫ mice demonstrated abnormal vascular findings including AVMs, while none of 15 Eng

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In children, severe to profound deafness results in poor long-term control of frequency and amplitude. Cochlear implantation restores control of amplitude only and implies the need for additional rehabilitative strategies for restoration of control of frequency.

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Children with cochlear implants developed their vocabularies at rates that were sufficient to prevent an increase in their gap indices as related to ideal scores at testing. A late age at implantation does not singularly preclude beneficial development of vocabulary.