C-kit expression and its function in mouse embryo

Abstract

In order to study the molecular mechanisms of histogenesis of the nervous system, it was focused on the c-kit, a proto-oncogene of the murine W locus, that is expressed not only in developing nervous cells, but also in fully matured neurons. Immunohistochemical analysis revealed that c-kit protein was detected in more diverse tissues which are phenotypically normal in W mutant mice, such as cerebrum, cerebellum, dorsal root ganglion cells, and plexus on digestive tubes. The role of c-Kit during embryogenesis was examined by means of in utero microinjection of an antagonistic anti-c-Kit monoclonal antibody. The offspring treated by the antibody were born with white spots, anemia and germ cell defects as well as W mutant mice. However, no obvious phenotypical defects of the neural tissues were observed except for the functional defect of the plexus on the digestive tract. These data suggest that c-kit may play important roles in the cell migration of melanoblasts, germ cells and the neural plexus on digestive tubes.

神経系の組織発生の分子機構を研究するために発育中の神経細胞内のみでなく、完全に成熟したニューロン内にも現れるネズミのW遺伝子座のプロトオンコジーンc-kitに注目した。免疫組織化学分析を利用して、c-kit蛋白質が、W突然変異ネズミ内における表現型上正常なさまざまな組織、たとえば大脳、小脳、後根神経節細胞および消化管の叢などで検出されることを明らかにした。拮抗的、抗c-kitモノクローナル抗体を子宮内に微量注入することによって、胚発生中のc-kitの役割を調べた。抗体によって治療した子供は、W突然変異ネズミと同様に白点、貧血および胚細胞欠陥を持って生まれた。しかしながら、消化管上の叢の機能的欠陥を除いては、神経組織の明らかな表現型欠陥は観察されなかった。これらのデータから、c-kitがメラニン芽細胞、胚細胞および消化管上の神経叢の細胞移動の重要な役割を果たしていることが明らかになった。