mAMBo · The role of ASCL1 and MYCN in human brain development
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2019-05-01 → 2021-04-30
- Финансиране от ЕС
- 212 934 €
- Участници
- 1
- Схема
- MSCA-IF-EF-ST
Линиите свързват координатора с партньорите.
Накратко на български
Ролята на гена MYCN при размножаването на стволови клетки в човешкия мозък се анализира чрез премахването му от тези клетки. Това помага за разбирането на механизмите, които определят развитието на мозъчната кора и причините за някои генетични нарушения.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
The role of ASCL1 and MYCN in human brain development
The human brain has largely expanded throughout evolution, and this is linked to an increased intelligence and cognition. In comparison to other mammals, humans have the ability to generate a greater number of neurons during brain development, as a result of changes in neural progenitors’ activity. In humans, these cells show an increased and prolonged proliferation that allow to maximise the number of cell divisions which, ultimately, will result in a higher number of neurons. Disruptions in the proliferative ability of neural progenitors, mainly due to genetic mutations, can lead to abnormal brain development and impaired brain functions. Therefore, unravelling the basic mechanisms driving neural progenitor expansion in humans will contribute to understand the developing brain in health and disease. Previous research has identified human-specific genes that are expressed in neural progenitors and are associated with the expansion of the brain. In this project, we proposed a parallel approach to focus on a gene already known for its role in the mouse brain, MYCN, which also appears mutated in patients with brain disorders. We aimed to study MYCN function by eliminating it from stem cells and assessing the effect of its loss in neural progenitor’s ability to expand and to form neurons. In conclusion, this project identified a novel function of MYCN in human neural progenitors, providing new insights towards the understanding of the developing cortex and its greater expansion in humans.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The evolutionary expansion of the neocortex in the primate lineage, and particularly in humans, underpins our higher cognitive abilities. Neural stem and progenitor cells (NPCs) show increased duration of proliferative phases in humans when compared to other mammals and particularly mice. However, the mechanisms responsible for these evolutionary differences in progenitor properties are poorly understood. In this study, I aim to explore the function of the ASCL1 and MYCN proteins in human NPCs. These two factors are crucial to promote proliferation in different NPC populations of the mouse forebrain, but their function in promoting proliferation of human NPCs, where they are broadly expressed, is not known. I will evaluate the spatio-temporal expression of ASCL1 and MYCN throughout human neocortical development and I will assess their cellular functions during NPC expansion using loss-of-function experiments. Finally, I will determine if ASCL1 and/or MYCN regulation have diverged between mouse and human to allow for the extended proliferative capacity of human NPCs. For this project, I will use human embryonic and fetal brain tissue and pluripotent stem cell-derived 2D neuronal and 3D spheroid cultures as in vitro models that recapitulate many aspects of human brain development. Together, this work will provide insights into the mechanisms regulating the duration of NPC expansion, a crucial parameter that underscores key differences in brain size between species, and will help to better assess the pathological mechanisms at the origin of neurodevelopmental diseases.
Оригинален текст от CORDIS (на английски).
Участници
- THE FRANCIS CRICK INSTITUTE LIMITED · LondonКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз