scholarly journals GnRH Neuronal Migration and Olfactory Bulb Neurite Outgrowth Are Dependent on FGF Receptor 1 Signaling, Specifically via the PI3K p110α Isoform in Chick Embryo

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 388-399 ◽  
Author(s):  
Youli Hu ◽  
Subathra Poopalasundaram ◽  
Anthony Graham ◽  
Pierre-Marc Bouloux
Keyword(s):  
Chick Embryo ◽  
Olfactory Bulb ◽  
Neurite Outgrowth ◽  
Neuronal Migration ◽  
Glycogen Synthase ◽  
Kallmann Syndrome ◽  
Pi3k Inhibitor ◽  
Fgf Signaling ◽  
In Ovo ◽  
Fgf Receptor

Fibroblast growth factor (FGF) signaling is essential for both olfactory bulb (OB) morphogenesis and the specification, migration, and maturation of the GnRH-secreting neurons. Disruption of FGF signaling contributes to Kallmann syndrome characterized by both anosmia and sexual immaturity. However, several unanswered questions remain as to which specific FGF receptor (FGFR)-1 signaling pathways are necessary for OB and GnRH neuronal development. Here, using pharmacological phosphatidylinositol 3-kinase (PI3K) isoform-specific inhibitors, we demonstrate a central role for the PI3K p110α isoform as a downstream effector of FGFR1 signaling for both GnRH neuronal migration and OB development. We show that signaling via the PI3K p110α isoform is required for GnRH neuronal migration in explant cultures of embryonic day (E) 4 chick olfactory placodes. We also show that in ovo administration of LY294002, a global PI3K inhibitor as well as an inhibitor to the PI3K p110α isoform into the olfactory placode of E3 chick embryo impairs GnRH neuronal migration toward the forebrain. In contrast, in ovo PI3K inhibitor treatment produced no obvious defects on primary olfactory sensory neuron axonal targeting and bundle formation. We also demonstrate that anosmin-1 and FGF2 induced neuronal migration of immortalized human embryonic GnRH neuroblast cells (FNC-B4-hTERT) is mediated by modulating FGFR1 signaling via the PI3K p110α isoform, specifically through phosphorylation of the PI3K downstream effectors, Akt and glycogen synthase kinase-3β. Finally, we show that neurite outgrowth and elongation of OB neurons in E10 chick OB explants are also dependent on the PI3K p110α isoform downstream of FGFR1. This study provides mechanistic insight into the etiology of Kallmann syndrome.

scholarly journals Regulation of Ribosomal S6 Protein Kinase-p90rsk, Glycogen Synthase Kinase 3, and β-Catenin in Early Xenopus Development

1999 ◽  
Vol 19 (2) ◽  
pp. 1427-1437 ◽  
Author(s):  
Monica A. Torres ◽  
Hagit Eldar-Finkelman ◽  
Edwin G. Krebs ◽  
Randall T. Moon
Keyword(s):  
Cell Fate ◽  
Glycogen Synthase ◽  
Dominant Negative ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Fgf Signaling ◽  
Fgf Receptor ◽  
Multifunctional Protein ◽  
Downstream Target ◽  
Cytoplasmic Proteins

ABSTRACT β-Catenin is a multifunctional protein that binds cadherins at the plasma membrane, HMG box transcription factors in the nucleus, and several cytoplasmic proteins that are involved in regulating its stability. In developing embryos and in some human cancers, the accumulation of β-catenin in the cytoplasm and subsequently the nuclei of cells may be regulated by the Wnt-1 signaling cascade and by glycogen synthase kinase 3 (GSK-3). This has increased interest in regulators of both GSK-3 and β-catenin. Searching for kinase activities able to phosphorylate the conserved, inhibitory-regulatory GSK-3 residue serine 9, we found p90 rsk to be a potential upstream regulator of GSK-3. Overexpression of p90 rsk in Xenopus embryos leads to increased steady-state levels of total β-catenin but not of the free soluble protein. Instead, p90 rsk overexpression increases the levels of β-catenin in a cell fraction containing membrane-associated cadherins. Consistent with the lack of elevation of free β-catenin levels, ectopic p90 rsk was unable to rescue dorsal cell fate in embryos ventralized by UV irradiation. We show that p90 rsk is a downstream target of fibroblast growth factor (FGF) signaling during early Xenopus development, since ectopic FGF signaling activates both endogenous and overexpressed p90 rsk . Moreover, overexpression of a dominant negative FGF receptor, which blocks endogenous FGF signaling, leads to decreased p90 rsk kinase activity. Finally, we report that FGF inhibits endogenous GSK-3 activity inXenopus embryos. We hypothesize that FGF and p90 rsk play heretofore unsuspected roles in modulating GSK-3 and β-catenin.

Fate of brachial muscles of the chick embryo innervated by inappropriate nerves: structural, functional and histochemical analyses

Development ◽  
1986 ◽  
Vol 95 (1) ◽  
pp. 147-168
Author(s):  
Jane Butler ◽  
Peter Cauwenbergs ◽  
Ethel Cosmos
Keyword(s):  
Chick Embryo ◽  
Muscle Growth ◽  
Extended Period ◽  
Differential Rate ◽  
Innervation Pattern ◽  
In Ovo ◽  
Intramuscular Nerve ◽  
Quantitative Analyses ◽  
Wing Bud ◽  
Actual Loss

The extent of interaction between brachial muscles and foreign (thoracic) nerves of the chick embryo was determined during an extended period of development in ovo from the perspectives of innervation pattern, function (motility analyses), muscle growth (quantitative analyses of muscle volume) and fibre-type expression (myosin-ATPase profiles). Results indicated that according to all parameters analysed, initially a compatible union existed between the foreign nerves and their muscle targets. During subsequent stages of development, deterioration of the once compatible relationship emerged, until eventually denervation of muscles, i.e. an actual loss of intramuscular nerve branches, was observed. The process of denervation, which proceeded at a differential rate among individual muscles, however was restricted to brachial muscles derived from the premuscle masses of the wing bud. In contrast, brachial muscles of myotomal origin were spared the fate of wing-bud-derived muscles and maintained a successful union with the foreign nerves.

scholarly journals Regulation of hepatic haem metabolism. Disparate mechanisms of induction of haem oxygenase by drugs and metals

1988 ◽  
Vol 250 (1) ◽  
pp. 189-196 ◽  
Author(s):  
B C Lincoln ◽  
J F Healey ◽  
H L Bonkovsky
Keyword(s):  
Chick Embryo ◽  
Primary Culture ◽  
In Ovo ◽  
Oxygenase Activity ◽  
Haem Oxygenase ◽  
Cytochrome P 450

We studied drug- and metal-mediated increases in activity of haem oxygenase, the rate-controlling enzyme for haem breakdown, in chick-embryo hepatocytes in ovo and in primary culture. Phenobarbitone and phenobarbitone-like drugs (glutethimide, mephenytoin), which are known to increase concentrations of an isoform of cytochrome P-450 in chick-embryo hepatocytes, were found to increase activities of haem oxygenase as well. In contrast, 20-methylcholanthrene, which increases the concentration of a different isoform of cytochrome P-450, had no effect on activity of haem oxygenase. Inhibitors of haem synthesis, 4,6-dioxoheptanoic acid or desferrioxamine, prevented drug-mediated induction of both cytochrome P-450 and haem oxygenase in embryo hepatocytes in ovo or in culture. Addition of haem restored induction of both enzymes. These results are interpreted to indicate that phenobarbitone and its congeners induce haem oxygenase by increasing hepatic haem formation. In contrast, increases in haem oxygenase activity by metals such as cobalt, cadmium and iron were not dependent on increased haem synthesis and were not inhibited by 4,6-dioxoheptanoic acid. We conclude that (1) induction of hepatic haem oxygenase activity by phenobarbitone-type drugs is due to increased haem formation, and (2) induction of haem oxygenase by drugs and metals occurs by different mechanisms.

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