Project description
Unravelling the mechanisms of cortical expansion in humans
Humans have exceptional skills and abilities relative to other mammals, even other primates, and larger neocortices. The neural progenitor cells (NPCs) that give rise to many, if not all, of the glial and neuronal cell types in the central nervous system have longer proliferative phases in humans than in other mammals, particularly mice. With the support of the Marie Skłodowska-Curie Actions programme, the mAMBo project is investigating the mechanisms behind this, focusing on the potential role of two proteins broadly expressed in humans and known to promote proliferation of NPCs in mice. Insight could shed light on the differences in brain sizes among species and point to potential mechanisms underlying neurodevelopmental diseases.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics
- medical and health sciences basic medicine anatomy and morphology
- natural sciences biological sciences developmental biology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
NW1 1AT London
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.