Molecular events in early development of the ciliary body: a question of folding

Ciliary body morphogenesis is a complicated, multi-step process requiring coordinated changes in cell shape, flexure of epithelial sheets and dynamic shifts in mitotic rates. Very little is known of how these cellular events are triggered or regulated. This review summarises current models of ciliary body morphogenesis. The role of intraocular pressure as a driver of morphogenesis is re-evaluated in the light of new information. An update on the role of the lens in ciliary body morphogenesis is presented. In the second part of the review current gene expression data is related to ciliary body morphogenesis. In particular the role of Bmp4 and its downstream target genes are discussed, with novel gene expression patterns of Bmp4 and Tgfbeta1i4 being presented.     

Elovl4 haploinsufficiency does not induce early onset retinal degeneration in mice

ELOVL4 was first identified as a disease-causing gene in Stargardt macular dystrophy (STGD3, MIM 600110.) To date, three ELOVL4 mutations have been identified, all of which result in truncated proteins which induce autosomal dominant juvenile macular degenerations. Based on sequence homology, ELOVL4 is thought to be another member within a family of proteins functioning in the elongation of long chain fatty acids. However, the normal function of ELOVL4 is unclear. We generated Elovl4 knockout mice to determine if Elovl4 loss affects retinal development or function. Here we show that Elovl4 knockout mice, while perinatal lethal, exhibit normal retinal development prior to death at day of birth. Further, postnatal retinal development in Elovl4 heterozygous mice appears normal. Therefore haploinsufficiency for wildtype ELOVL4 in autosomal dominant macular degeneration likely does not contribute to juvenile macular degeneration in STGD3 patients. We found, however, that Elovl4+/- mice exhibit enhanced ERG scotopic and photopic a and b waves relative to wildtype Elovl4+/+ mice suggesting that reduced Elovl4 levels may impact retinal electrophysiological responses.     

Pathogenesis and therapy of cutaneous lymphomas – Progress or impasse?

The cutaneous environment hosts a number of hematopoietic neoplasms that are dominated by primary cutaneous (PC) T-cell lymphomas. Recent progress in molecular biology and immunology has provided tools to investigate the pathogenesis and the biology of these neoplasms. This review highlights newest findings concerning the immune biology of CD4+ CD56+ hematodermic neoplasms, and PC T-cell and B-cell lymphomas, speculating how these can be translated into more sophisticated, biology-based treatment approaches in the near future.     

Cholesterol-enriched diet affects spatial learning and synaptic function in hippocampal synapses

The aim of the present study was to determine the effect of a cholesterol-rich diet on learning performance and monitor possible related changes in synaptic function. To this purpose, we compared controls with rats fed with a cholesterol-enriched diet (CD). By using a Morris water-maze paradigm, we found that CD rats learned a water-maze task more quickly than rats fed with a regular diet (RD). A longer period of this diet tended to alter the retention of memory without affecting the improvement in the acquisition of the task. Because of the importance of the hippocampus in spatial learning, we hypothesized that these behavioral effects of cholesterol would involve synaptic changes at the hippocampal level. We used whole-cell patch-clamp recording in the CA1 area of a hippocampal rat slice preparation to test the influence of the CD on pre- and postsynaptic function. CD rats displayed an increase in paired-pulse ratio in both glutamatergic synapses (+48 +/- 9%) and GABAergic synapses (+41 +/- 8%), suggesting that the CD induces long-lasting changes in presynaptic function. Furthermore, by recording NMDA-receptor-mediated currents (I(NMDA)) and AMPA-receptor-mediated currents (I(AMPA)) in the same set of cells we found that CD rats display a lower I(NMDA)/I(AMPA) ratio (I(NMDA)/I(AMPA) = 0.75 +/- 0.32 in RD versus 0.10 +/- 0.03 in CD), demonstrating that cholesterol regulates also postsynaptic function. We conclude that a cholesterol-rich diet affects learning speed and performance, and that these behavioral changes occur together with robust, long-lasting, synaptic changes at both the pre- and postsynaptic level.     

Adrenaline contributes to prenatal respiratory maturation in rat medulla-spinal cord preparation

Adrenaline is a potent respiratory regulator. However, adrenergic contribution to the developing respiratory center has not been studied extensively. Adrenaline application on embryonic day 17 medulla-spinal cord block preparations abolished non-respiratory activity and enhanced respiratory frequency. Phentolamine application on neonatal blocks that produced stable neonatal respiration resulted in respiratory destabilization. These results suggest that central adrenergic modulation is involved in fetal respiratory development and maintenance of stable respiration.     

Growing axons in fish optic nerve are accompanied by astrocytes interconnected by tight junctions

Mammalian astrocytes are in general interconnected by gap but not by tight junctions and play an ambiguous and controversially discussed role in central nervous system regeneration. At different neuroanatomical sites, fish astrocytes are interconnected by tight junctions and desmosomes and are involved in the successful regeneration of lesioned fiber tracts. In fish, newly generated retinal ganglion cells continuously grow new axons to the optic tectum but the interrelationship between glial tight junctions and axonal growth is undefined so far. We therefore investigated the occurrence of tight junctional structures and molecules within the ribbon-shaped optic nerve of a teleost fish (Astatotilapia burtoni) and found a predominant expression of zonula occludens protein-1 and claudin-1 in astrocytes where axons of new ganglion cells are assembled retinotopically within the optic nerve. This may support a previously formulated hypothesis according to that different properties of astrocytic membranes could be responsible for different glio-neuronal interactions which in turn may determine the micro-environmental conditions of growing axons.     

Development of the corticospinal tract in the mouse spinal cord: a quantitative ultrastructural analysis

The growth of corticospinal tract (CST) axons was studied quantitatively at the 7th cervical (C7) and the 4th lumbar (L4) spinal segments in the balb/cByJ mice at the ages of postnatal day (P) 0, 2, 4, 6, 8, 10, 14, and 28. The cross-sectional area of the CST increased progressively with time. Unmyelinated axons, the most prominent CST element during early development, reached maximum at C7 and L4 on P14. Two phases of increase in the number of unmyelinated axons were observed at C7, while only one surge of axonal outgrowth was found at the L4 level. Pro-myelinated axons, defined as axons surrounded by only one layer of oligodendrocytic process, were first seen at P2 and P4 in the C7 and the L4 level, respectively, followed by a dramatic increase in the number of myelinated axons from P14 onwards at both spinal levels. Myelination of the CST axons occurred topographically in a dorsal-to-ventral pattern. The number of growth cones increased rapidly at the C7 level to reach its maximum at P4, while those at L4 increased steadily to the peak at P10. Growth cones with synapse-like junctions were occasionally observed in the growing CST. Degenerating axons and growth cones partly accounted for the massive axon loss at both spinal segments during CST development. Overall, the mouse CST elements changed dynamically in numbers during postnatal development, suggesting a vigorous growing and pruning activity in the tract. The mouse CST also showed a similar growth pattern to that of the rat CST.