Поиск и изучение транскрипционных факторов, регулирующих экспрессию гомеобоксного гена Xanf-1 в развитии головного мозга у шпорцевой лягушки

Выяснение молекулярно-генетических механизмов раннего развития головного мозга — одна из фундаментальных задач функциональной геномики. Знание этих механизмов так же важно для понимания природы многих наследственных заболеваний у человека.

Среди всех отделов головного мозга в наименьшей степени изучены механизмы развития т.н. переднего мозга. Вместе с тем, выяснение именно этих механизмов крайне важно ввиду того, что передний мозг отвечает за высшие формы нервной деятельности, в том числе, за мышление у человека. Кроме того, передний мозг является одним из основных анатомических признаков, отличающих позвоночных животных от всех других организмов. Поэтому изучение механизмов его развития важно для понимания особенностей эволюции типа позвоночных животных в целом.

Эффективным подходом к решению указанной задачи может быть поиск и изучение функций регуляторных белков, определяющих пространственно-временное «расписание» дифференцировки клеток в зачатке переднего мозга.

Ранее, в группе молекулярных основ эмбриогенеза ИБХ РАН, был идентифицирован новый класс гомеодоменных транскрипционных факторов, Ап^ ответственных за наиболее раннюю стадию развития зачатка переднего мозга (2ага1зку е1 а1., 1992; 2ага1зку а1., 1995; Кагашкауа е1 а1., 1997). На модели эмбрионов шпорцевой лягушки было показано, что представитель данного класса транскрипционных факторов, ХапМ, играет ключевую роль в развитии зачатка переднего мозга, а искусственно вызванная активация Хап/-1 вне зоны его нормальной экспрессии — в передней части нервной пластинкиприводит к серьезным аномалиям переднего мозга (БаИаш & а1., 1998; Егшакоуа е1 а1., 1999).

В связи с этим, актуальной задачей является поиск и изучение функций специфических транскрипционных факторов, обеспечивающих строгую пространственную локализацию экспрессии Хап/-1 в границах будущего зачатка переднего мозга.

Поскольку решение данной задачи сопряжено со значительными трудностями, обусловленными, прежде всего, малыми размерами раннего зачатка переднего мозга и, как следствие, весьма низкой копийностью искомых транскрипционных факторов, актуальной технической задачей является разработка методики, позволяющей проводить систематический поиск таких факторов с помощью экспрессионных кДНК библиотек эмбриональных клеток.

Решение этих двух задач представляется важным не только для выяснения механизмов, контролирующих экспрессию одного из ключевых регуляторов дифференцировки переднего мозга, гена Хап/-1, но и с точки зрения разработки универсальных подходов к изучению механизмов регуляции экспрессии генов в индивидуальном развитии.

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