Int-2 influences the development of the nodose ganglion

F Qin, ML Kirby - Pediatric research, 1995 - nature.com
F Qin, ML Kirby
Pediatric research, 1995nature.com
The int-2 gene was first described as a common proviral integration site in tumors induced
by mouse mammary tumor virus (MMTV). During embryonic development int-2 is produced
and released by cells in the rhombencephalon and diffuses to the ectoderm to induce
formation of the otocyst from the otic placode. Int-2 also influences the development of the
vestibulocochlear ganglion that is derived from the otic placode. During embryogenesis the
otic and nodose placodes, primordia of the inner ear and the nodose ganglia, respectively …
Abstract
The int-2 gene was first described as a common proviral integration site in tumors induced by mouse mammary tumor virus (MMTV). During embryonic development int-2 is produced and released by cells in the rhombencephalon and diffuses to the ectoderm to induce formation of the otocyst from the otic placode. Int-2 also influences the development of the vestibulocochlear ganglion that is derived from the otic placode. During embryogenesis the otic and nodose placodes, primordia of the inner ear and the nodose ganglia, respectively, are located adjacent to each other in the embryonic ectoderm. The nodose ganglia provide sensory innervation to all of the viscera. Using Northern analysis we determined that a high level of int-2 is transcribed in stage 14 chick embryos. This is the time when cells begin to migrate from the nodose placodes to form the nodose ganglia. Using human and mouse sequences to design primers around the translation start site of the transcript, a partial clone containing the translation start site of chick int-2 was obtained by polymerase chain reaction amplification from chick genomic DNA and cloned. An antisense oligodeoxynucleotide was designed to the region of the translation start site, and in vitro and in vivo techniques were used to demonstrate that inhibition of int-2 translation using this antisense oligonucleotide causes delayed and abnormal development of the nodose placodes. For in vitro studies, explants of stage 12 chick embryos containing neural tube, adjacent surface ectoderm, and pharyngeal endoderm were cultured with int-2 antisense oligonucleotide. For the in vivo studies, pieces of resin impregnated with int-2 antisense oligonucleotide were implanted into the neural tube of stage 12 chick embryos at the level of the otic and nodose placodes. We found that the development of the nodose placodes exposed to int-2 antisense oligodeoxynucleotide was delayed and abnormal. These differences were not seen in embryos or explants treated with similar concentrations of sense or nonspecific oligomers. Western analysis and immunohistochemistry showed that an int-2-immunoreactive protein was reduced in the pharyngeal region and nodose ganglia of the embryos exposed to int-2 antisense oligodeoxynucleotide, whereas it was not affected in embryos treated with sense oligomer. We conclude that int-2 may be necessary for normal development of the nodose ganglia.
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