Summary
This research project aims to define the molecular mechanisms governing progenitor balance and neuronal connectivity in the developing cerebral cortex, investigating how disruptions contribute to human neurodevelopmental disorders.
DEFINING MECHANISMS OF PROGENITOR BALANCE AND NEURONAL CONNECTIVITY
US · IL
NIH
grant
awarded
#nih-5R35NS116859-06
What they want
The project focuses on understanding how radial progenitors coordinate neuron generation and placement, and how the balance between radial and intermediate progenitors is maintained. It seeks to define the molecular logic behind progenitor balance and projection neuronal connectivity, which is currently an enigma. Specific aims include discovering how progenitor balance is achieved, defining primary cilia-mediated mechanisms guiding neuronal growth and connectivity, and determining how changes in these processes cause cortical malformations underlying neurodevelopmental disorders such as microcephaly, macrocephaly, lissencephaly, epilepsy, schizophrenia, and autism spectrum disorders.
Deliverables
- Discovery of how the developmental balance between radial and intermediate progenitors is achieved.
- Definition of primary cilia-mediated mechanisms guiding projection neuronal growth and connectivity.
- Determination of how changes in developmental processes can cause cortical malformations underlying human neurodevelopmental disorders.
Technical requirements
- Combined application of progenitor or neuron type specific mouse genetic models
- Live imaging
- Lineage tracing
- Mapping of signaling interactomes
- Optogenetic and chemogenetic manipulation of primary cilia signaling
- Single cell genomics
- Functional evaluation of human mutations associated with neurodevelopmental disorders
