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Semaphorin 3F is critical for development of limbic system circuitry and is required in neurons for selective CNS axon guidance events.

Little is known about the role of class 3 semaphorins in the development of CNS circuitry. Several class 3 semaphorins, including semaphorin 3F (Sema3F) bind to the receptor neuropilin-2 to confer chemorepulsive responses in vitro. To understand the role of Sema3F in the establishment of neural circuitry in vivo, we have generated sema3F null and sema3F conditional mutant mice. Inspection of the peripheral nervous system in sema3F null mice reveals that Sema3F is essential for the proper organization of specific cranial nerve projections. Analysis of the CNS in sema3F null mice reveals a crucial role for Sema3F in the rostral forebrain, midbrain, and hippocampus in establishing specific Npn-2 (neuropilin-2)-expressing limbic tracts. Furthermore, we identify Sema3F and Npn-2 as the first guidance cue-receptor pair shown to be essential for controlling the development of amygdaloid circuitry. In addition, we provide genetic evidence in vertebrates for a neuronal requirement of a soluble axon guidance cue in CNS axon guidance. Our data reveal a requirement for neuronal Sema3F in the normal development of the anterior commissure in the ventral forebrain and infrapyramidal tract in the hippocampus. Thus, our results show that Sema3F is the principal ligand for Npn-2-mediated axon guidance events in vivo and is a critical determinant of limbic and peripheral nervous system circuitry.

Amygdala↗

Expression of the c-Harvey ras oncogene alters peptide synthesis in the neurosecretory cell line AtT20.

Ras proteins are enriched in neurosecretory cells suggesting that ras may play an important role in regulating the differentiated properties of such cells. We introduced the human H-ras oncogene, EJ-ras, into the model secretory cell line AtT20 to determine the effects of ras oncogene expression on neuropeptide synthesis and release. We report here that both of these processes are changed in ras-transfected AtT20 cells. Stimulated release of the pituitary hormone corticotropin is reduced, and transcription of the gene encoding its precursor, proopiomelanocortin, is down-regulated. At the same time, expression of other genes, both housekeeping and neural-specific, remain relatively unchanged. The alteration of proopiomelanocortin expression in AtT20 cells following ras oncogene transformation supports the hypothesis that ras may play a role in the determination of the differentiated phenotype of neurosecretory cells.

Actins↗

Neuronal ectopia in tiger retina.

Ocular pathology in a ten week-old tiger is described. In the retinae of both glaucomatous eyes, venous congestion and scattered hemorrhages were observed; rare perivascular infiltrates were seen. The basal lamina of the inner limiting membrane was considerably thickened, and serous exudates were widely distributed within the vitreous body. The retina was studied with a series of specific antibodies. Müller (glial) cells were well developed and could be immuno-labelled by antibodies against both vimentin and glial fibrillary protein (GFAP). Neurofilament-specific antibodies revealed the presence of ganglion and horizontal cells, and of a nerve fibre layer which was unusually distant from the inner limiting membrane. Within both plexiform layers, scattered neuronal cells were found. The most important finding was the presence of cells between the nerve fibre layer and the inner limiting membrane, which could be immuno-labelled by neuron-specific antibodies, and which expressed thy typical morphology of migrating neuroblasts. It is suggested that this neuronal ectopia might be due to an inflammatory related reactive change in Müller cells which, in turn, might have lost their orderly guiding function for migrating neuroblasts.

Animals↗

[Correlation between synaptic protein phosphorylation in hippocampi and shuttle box avoidance behavior].

The present investigation was undertaken to detect whether protein phosphorylation levels of hippocampal synaptosomes in mice trained on shuttle box avoidance task would show some changes. The synaptosomes were prepared at different times after the conclusion of training and labelled with gamma-32P-ATP for in vitro determination. The results are as follows: (1) No significant differences were found in the phosphorylation of synaptosomal proteins in different brain areas in normal mice before training. (2) Immediately after the conclusion of shuttle box avoidance task there appears a correlation between protein phosphorylation levels in hippocampal synaptosomes and the degree of success of training. (3) 24 h after the completion of training the above relationship is more significant, and protein phosphorylation levels of right hippocampus in Good Score Group is markedly higher than that of left one, but in the Inferior Score Group, the left-right difference is reverse. The formation of such asymmetry in protein phosphorylation in hippocampi is unknown. These data indicate that the synaptic protein phosphorylation in hippocampi might be a molecular mechanism of acquisition.

Animals↗

[The prognostic value of human neuroendocrine clone on colorectal carcinoma].

OBJECTIVE: To demonstrate the prognostic value of neuroendocrine clone on colorectal carcinoma. METHODS: The immunochemistry methods were used to investigate the percent of neuroendocrine carcinoma in 73 human colorectal carcinoma. Retrospective analysis and follow-up were carried out in all patients. RESULTS: In all 73 cases of colorectal carcinoma, the total percentage of neuroendocrine carcinoma was 17.8%. Neuroendocrine carcinoma included 11 synapse positive, 6 chromogranin positive and 4 both positive. The major factors related to the prevalence of neuroendocrine carcinoma were sex, age, tumor location and Dukes' stage. And the 1-year survival rate of the patients who suffered from neuroendocrine carcinoma is obviously lower than that of other colorectal carcinoma. CONCLUSIONS: The neuroendocrine carcinoma is a special kind of human colorectal carcinoma, and neuroendocrine clone may be a new marker of the malignant potency. The neuroendocrine clone has its prognostic value and may be a novel therapeutic target.

Adult↗

Activation of multifunctional Ca2+/calmodulin-dependent protein kinase in GH3 cells.

We report that the rat pituitary cell line GH3 contains a Ca2(+)- and calmodulin-dependent protein kinase with properties characteristic of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) from rat brain. The GH3 kinase exhibits the hallmark of authentic CaM kinase: conversion from Ca2(+)-dependent to Ca2(+)-independent activity following a brief initial phosphorylation in vitro. This phosphorylation occurs at a site which is similar or identical to that of the "autonomy" site of the rat brain enzyme and thus may be an autophosphorylation event. GH3 CaM kinase is phosphorylated and becomes Ca2(+)-independent in situ. Depolarization of intact cells with K+ opens calcium channels and leads to the phosphorylation of CaM kinase at the autonomy site, and the kinase becomes significantly and persistently Ca2(+)-independent. Treatment of cells with thyrotropin-releasing hormone (TRH), which activates the phosphatidylinositol signaling pathway, also generates a Ca2(+)-independent CaM kinase in situ. The primary effect of TRH on CaM kinase activity is transient and correlates with the spike of Ca2+ released from intracellular stores and the rapid phase of prolactin release from GH3 cells. This study demonstrates that CaM kinase is able to detect and respond to both calcium that enters the cell through voltage-sensitive Ca2+ channels and calcium released from internal stores via the phosphatidylinositol pathway. We find that TRH, a hormone that causes release of prolactin and was previously believed to activate primarily protein kinase C, also significantly activates CaM kinase in intact cells.

Animals↗