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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2011-8-18
pubmed:abstractText
When and how newborn neurons are organized to form a functional network in the developing brain remains poorly understood. An attractive model is the gonadotropin-releasing hormone (GnRH) neuron system, master regulator of the reproductive axis. Here we show that blockage of IGF signaling, a central growth-promoting signaling pathway, by the induced expression of a dominant-negative form of IGF1 receptor (IGF1R) or specific IGF1R inhibitors delayed the emergence of GnRH2 neurons in the midbrain and GnRH3 neurons in the olfactory bulb region. Blockage of IGF signaling also resulted in an abnormal appearance of GnRH3 neurons outside of the olfactory bulb region, although it did not change the locations of other olfactory neurons, GnRH2 neurons, or brain patterning. This IGF action is developmental stage-dependent because the blockade of IGF signaling in advanced embryos had no such effect. An application of phosphatidylinositol 3-kinase (PI3K) inhibitors phenocopied the IGF signaling deficient embryos, whereas the MAPK inhibitors had no effect, suggesting that this IGF action is mediated through the PI3K pathway. Real-time in vivo imaging studies revealed that the ectopic GnRH3 neurons emerged at the same time as the normal GnRH3 neurons in IGF-deficient embryos. Further experiments suggest that IGF signaling affects the spatial distribution of newborn GnRH3 neurons by influencing neural crest cell migration and/or differentiation. These results suggest that the IGF-IGF1R-PI3K pathway regulates the precise temporal and spatial organization of GnRH neurons in zebrafish and provides new insights into the regulation of GnRH neuron development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11814-24
pubmed:meshHeading
pubmed-meshheading:21849542-Animals, pubmed-meshheading:21849542-Animals, Genetically Modified, pubmed-meshheading:21849542-Cell Differentiation, pubmed-meshheading:21849542-Cell Movement, pubmed-meshheading:21849542-Female, pubmed-meshheading:21849542-Gonadotropin-Releasing Hormone, pubmed-meshheading:21849542-Hot Temperature, pubmed-meshheading:21849542-Male, pubmed-meshheading:21849542-Mesencephalon, pubmed-meshheading:21849542-Neurogenesis, pubmed-meshheading:21849542-Neurons, pubmed-meshheading:21849542-Olfactory Bulb, pubmed-meshheading:21849542-Pyrrolidonecarboxylic Acid, pubmed-meshheading:21849542-Signal Transduction, pubmed-meshheading:21849542-Somatomedins, pubmed-meshheading:21849542-Time Factors, pubmed-meshheading:21849542-Zebrafish, pubmed-meshheading:21849542-Zebrafish Proteins
pubmed:year
2011
pubmed:articleTitle
Regulation of temporal and spatial organization of newborn GnRH neurons by IGF signaling in zebrafish.
pubmed:affiliation
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't