NEURALSTEMSCREEN · A mosaic screen for genes regulating neural stem cell divisioins in the developing adult central nervous system of Drosophila
6РП — Действия „Мария Кюри“
- Период
- 2004-06-17 → 2006-06-16
- Финансиране от ЕС
- 167 665 €
- Участници
- 1
- Схема
- EIF
Линиите свързват координатора с партньорите.
Накратко на български
Гените, които контролират деленето на нервните стволови клетки при плодовите мухи, определят кога те спират да създават нови неврони. Разбирането на този процес помага при разработването на терапии за мозъчни наранявания и невродегенеративни заболявания.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - NEURALSTEMSCREEN (A mosaic screen for genes regulating neural stem cell divisions in the developing adult central nervous system of Drosophila)
Neural stem cells generate all of the neurons in the adult brain during embryonic and fetal development. Studying how these stem cells divide to produce different types of neurons is critical for understanding how of human and animal brain size is regulated. It is also of fundamental importance for developing safe and efficient stem-cell based therapies for treating neurodegenerative diseases and brain injuries. More specifically, identifying the factors that trigger neural stem cells from starting and stopping to divide allows the accurate prediction of neuronal numbers generated by each treatment regime. The fruitfly Drosophila shares app.75% of important genes with humans and its brain is also constructed from neural stem cell-like progenitor cells (called neuroblasts). Therefore, the sophisticated genetic techniques available in Drosophila provide a powerful way of modelling some aspects of mammalian brain growth and development. We conducted large-scale genetic screens of over 3000 Drosophila genes, searching for those that are necessary for the correct start and stop of neuroblast divisions. We found 16 genes that are required for neuroblasts to divide at the normal rate and 52 genes that instruct neuroblasts when to stop dividing. Interestingly, several genes appear to function by altering the structure of neuroblast chromatin, the material composed of DNA and proteins packaged into chromosomes. In parallel to the genetic screen, we found that two proteins that bind to DNA (transcription factors), also regulate the time at which neuroblasts stop dividing, thereby influencing final brain size. Remarkably mutations in these two genes induce neuroblasts to continue dividing for much longer than normal, leading to new neurons being added to the adult brain. This study identifies a global mechanism for coordinating the number of neurons with the type of neurons generated by a neural stem cell.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Neural stem cells have the capacity to generate vast numbers of neuronal progeny over long periods of time when cultured in vitro, yet during normal development this mitotic potential must be kept in check so that each region of the central nervous system contains the appropriate number of neurons and glia. As neural stem cells have the remarkable capacity of regenerating the damaged brain, understanding the developmental regulation of their divisions may have important implications for future stem cell-based therapies. The remodelling of the Drosophila central nervous system (CNS) from its larval to adult form provides a genetically tractable system for studying region-specific proliferation at the level of individual neural stem cells, termed neuroblasts. Using in vivo clonal analysis, our lab recently explored the nature of the stop mechanism limiting how many times a postembryonic neuroblast (pNB) can divide. These studies have identified a pathway linking a conserved family of positional information genes, the Hox genes, to the developmental time at which neural proliferation ceases. The purpose of my project is to conduct a genome-wide mosaic screen to identify new genes that are also involved in regulating neural stem cell divisions.This will take advantage of several genetic tools and particular strains of Drosophila that have been developed in the host laboratory recently. New stem cell division genes will be characterised at the genetic and molecular level and their vertebrate orthologues studied in the context of hindbrain development.
Оригинален текст от CORDIS (на английски).
Участници
- MEDICAL RESEARCH COUNCIL · LONDONКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз