A TRANSGENIC NEUROANATOMICAL MARKER IDENTIFIES CRANIAL NEURAL CREST DEFICIENCIES ASSOCIATED WITH THE PAX3 MUTANT SPLOTCH

The murine Pax3 gene encodes a transcription factor containing a paired domain as well as a paired-type homeodomain. Its expression during embryonic development is temporally and spatially restricted, including mainly the dorsal part of the neural tube, the mesencephalon, the neural crest derivatives, and the dermomyotome. Development in the absence of Pax3 can be studied in Splotch mutant mice, which bear mutations within the Pax3 gene. Various alleles have been phenotypically and molecularly characterized. Abnormalities have been observed in the brain, the neural tube, the trunk neural crest derivatives and in muscles of these mutants. The importance of PAX3 during human embryonal development is readily seen in Waardenburg patients, who present a dominant inherited syndrome consisting mainly of craniofacial abnormalities, pigmentation deficiencies, and deafness, consecutive to PAX3 mutations. In order to analyze the nervous system of Splotch embryos in more detail, we employed the transgenic mouse line L17. These transgenic mice harbor a beta-galactosidase marker gene under the control of Hoxa-7 promoter elements. Probably in combination with cis-elements adjacent to the integration site of the L17 transgene, the Hoxa-7 elements drive the expression of the marker gene in major parts of the peripheral nervous system, as well as in more restricted parts of the central nervous system. These structures can be visualized during embryonic development, allowing detailed neuroanatomical studies in midgestation embryos. We describe the beta-galactosidase expression in wild-type L17 mice and demonstrate the applicability of L17 mice to the study of the nervous system. We then apply this experimental system to the analysis of Splotch embryos. Our findings underline the importance of Pax3 in the development of neural crest-derived structures, especially of cranial ganglia and nerves. We suggest the use of L17 mice as a valuable tool to perform similar analysis for other embryonal mutant phenotypes. (C) 1985 Academic Press, Inc.