Int-2 influences the development of the nodose ganglion

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.(ABSTRACT TRUNCATED AT 250 WORDS)