# DEFINING MECHANISMS OF PROGENITOR BALANCE AND NEURONAL CONNECTIVITY

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $544,250

## Abstract

Principal Investigator (Last, First, Middle): Anton, Eva S.
PROJECT SUMMARY
Radial progenitors serve as an instructive matrix to coordinate the generation and placement of
appropriate number and types of neurons in the developing cerebral cortex. Radial progenitors
divide asymmetrically to generate neurogenic intermediate progenitors (IPs) and the symmetric
proliferation of IPs serves to rapidly expand cortical neuronal population. The dynamic
maintenance of the balance between radial and intermediate progenitors is of fundamental
importance to the generation of right number and types of projection neurons at the right time
in the cerebral cortex. Once generated, growth and connectivity of cortical neurons enables the
formation of basic neuronal circuitry in the cerebral cortex. The balanced diversity of cortical
progenitors and the resultant generation, placement, and connectivity of projection neurons
thus serve as a blueprint to guide the formation of an appropriately wired cerebral cortex.
Disruptions in these essential features of the developing cerebral cortex are at the core of many
human neurodevelopmental disorders including microcephaly, macrocephaly, lissencephaly,
epilepsy, schizophrenia, and autism spectrum disorders. However, the molecular logic that
instructs progenitor balance and projection neuronal connectivity remains an enigma. This
proposal aims to remedy this gap in our understanding of cerebral cortical formation. In
particular, (1) we will discover how the developmental balance between radial and intermediate
progenitors, vital for the production of right number and types of cortical neurons at the right
time, is achieved, (2) define hitherto uncharted, primary cilia-mediated mechanisms guiding
projection neuronal growth and connectivity, and (3) determine how changes in these
developmental processes can cause cortical malformations underlying human
neurodevelopmental disorders. We aim to make these goals attainable by using an innovation
driven approach that involves combined application of latest advances in 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, and functional evaluation of human mutations associated with neurodevelopmental
disorders. Understanding how progenitors and neurons are assembled, organized, and
connected appropriately to facilitate cerebral cortical formation, offers us the opportunity to
rethink and redraw the rules of corticogenesis in the service of better diagnostic and therapeutic
insights into neurodevelopmental disorders.

## Key facts

- **NIH application ID:** 9986311
- **Project number:** 1R35NS116859-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** EVA S ANTON
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $544,250
- **Award type:** 1
- **Project period:** 2020-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986311

## Citation

> US National Institutes of Health, RePORTER application 9986311, DEFINING MECHANISMS OF PROGENITOR BALANCE AND NEURONAL CONNECTIVITY (1R35NS116859-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9986311. Licensed CC0.

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