During development, growth cones can be guided at a distance by diffusible factors, which are attractants and/or repellents. The semaphorins are the largest family of repulsive axon guidance molecules. Secreted semaphorins bind neuropilin receptors and repel sensory, sympathetic, motor, and forebrain axons. We found that in rat embryos, the olfactory epithelium releases a diffusible factor that repels olfactory bulb axons. In addition, Sema A and Sema IV, but not Sema III, Sema E, or Sema H, are able to orient in vitro the growth of olfactory bulb axons; Sema IV has a strong repulsive action, whereas Sema A appears to attract those axons. The expression patterns of sema A and sema IV in the developing olfactory system confirm that they may play a cooperative role in the formation of the lateral olfactory tract. This also represents a further evidence for a chemoattractive function of secreted semaphorins.

OBJECTIVE-We sought to identify genes with differential expression in cerebral cavernous malformations (CCMs), arteriovenous malformations (AVMs), and control superficial temporal arteries (STAs) and to confirm differential expression of genes previously implicated in the pathobiology of these lesions. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript METHODS-Total ribonucleic acid was isolated from four CCM, four AVM, and three STA surgical specimens and used to quantify lesion-specific messenger ribonucleic acid expression levels on human gene arrays. Data were analyzed with the use of two separate methodologies: gene discovery and confirmation analysis. RESULTS-The gene discovery method identified 42 genes that were significantly up-regulated and 36 genes that were significantly down-regulated in CCMs as compared with AVMs and STAs (P = 0.006). Similarly, 48 genes were significantly up-regulated and 59 genes were significantly down-regulated in AVMs as compared with CCMs and STAs (P = 0.006). The confirmation analysis showed significant differential expression (P < 0.05) in 11 of 15 genes (angiogenesis factors, receptors, and structural proteins) that previously had been reported to be expressed differentially in CCMs and AVMs in immunohistochemical analysis. CONCLUSION-We identify numerous genes that are differentially expressed in CCMs andAVMs and correlate expression with the immunohistochemistry of genes implicated in cerebrovascular malformations. In future efforts, we will aim to confirm candidate genes specifically related to the pathobiology of cerebrovascular malformations and determine their biological systems and mechanistic relevance. KeywordsArteriovenous malformations; Cavernous malformations; Gene arrays; Gene expression Cerebrovascular malformations (CVMs) are lesions with an abnormal vessel phenotype that predisposes patients to hemorrhagic strokes, seizures, focal neurological deficits, and other clinical manifestations (4,22). They include arteriovenous malformations (AVMs) and cerebral cavernous malformations (CCMs) and have distinct clinicopathological radiological profiles (14,30). The AVMs are tangled complexes of tortuous vessels representing fistulous connections between arteries and veins, and they lack an intervening capillary bed. They reveal preserved features of mature vessel wall phenotype altered by high flow and hemodynamic stress, including arterial, nidal, and venous aneurysms (5,6,28). The CCMs are characterized by caverns filled with blood or thrombus and are lined with a single layer of endothelial cells. These low-flow lesions are associated with brittle vasculature and repetitive oozing (5,6). The CCMs lack inter-endothelial cell tight junctions and mature vessel wall angio-architecture (8, 37).Little is known about the mechanisms of genesis or the progression of these lesions. Several proteins are abnormally expressed in AVMs and CCMs. Our group and others have demonstrated by performing immunohistochemical analysis that vascular endoth...

We have recently described a female patient with myotubular myopathy (MTM1) and an interstitial deletion at Xq28. Characterisation of the deletion allowed us to position the MTM1 gene to a 600 kb region between DXS304 and DXS497. In order to further restrict the region we screened for deletions in a set of 38 patients. We found two overlapping deletions in boys that in addition to MTM1 showed an unexpected abnormal genital development. As the latter phenotype is not found in the other non-deleted MTM1 patients, our observations are best explained by a contiguous gene syndrome. The deletions define a 430 kb region that contains the MTM1 gene and most likely a gene implicated in male sexual development. A high resolution physical map of this region is presented.