Примеры узкой специфичности

Эти примеры узкой специфичности связей и на более, и на менее продвинутых стадиях развития убедили нас, что на поверхности эмбриональных аксонов появляются определенные молекулы, обеспечивающие распознавание, что существует много разных типов таких молекул и что растущие нейроны направляются к клеткам-мишеням благодаря избирательной адгезии своих филоподий с помеченными соответствующим образом аксонами. Они привели нас также к мысли о том, что небольшие группы нейронов, чьи аксоны следуют вместе, могут нести одинаковые молекулы распознавания.

Один из способов обнаружить гипотетические молекулы распознавания — применить иммунологические методы. Если эмбриональные клетки саранчи ввести мыши, то ее иммунная система отреагирует на это продуцированием антител ко всем молекулам, находящимся на поверхностях чужих клеток. При этом каждое антитело специфически связывается только с одной определенной молекулой — соответствующим ему антигеном. Применяя методику так называемых моноклональных антител и «просеивая» тысячи полученных препаратов, можно, наконец, найти антитело, специфичное для молекулы, экспрессия которой и по времени, и пространственно коррелирует с выбором, совершаемым данным конусом роста. Такая молекула с большой долей вероятности и будет одной из тех меток, по которым клетки распознают друг друга. Для подобной работы 8-дневные эмбрионы саранчи наиболее удобны. На этой стадии развития нервные клетки еще не продуцируют медиаторов, или, скажем, белков, свойственных дифференцированным нейронам на более поздних стадиях. В основном происходит образование конусов роста и определение путей, по которым им дальше следует расти. Мы надеялись, что с таким материалом будет легче получить ан

титела именно к молекулам, участвующим в межнейронном распознавании.

К. Котрла инъецировала мышам клетки нейроэпителия 8-дневного эмбриона саранчи, получала гнбридомы (путем слияния клеток мышиной селезенки с миеломнымн клетками) и проверяла их способность синтезировать антитела к антигенам поверхности нейронов. Она нашла несколько моноклональных антител, которые связывались с поверхностью только немногих и притом растущих в одних пучках аксонов, что и предсказывалось в предлагаемой нами гипотезе. Два таких антитела, связывались с поверхностью только одного нервного пучка как на стадии 8- дневного эмбриона, когда пучков 25, так и на стадии 6,5-дневного эмбриона, когда их только 3.

 

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