# Developmental Timing During Cortical Development

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $421,489

## Abstract

Summary/Abstract
 The human cerebral cortex contains an astonishing diversity of cell types distributed across dozens of
functional areas, which emerge during early development for an apparently uniform neuroepithelium. It has long
been hypothesized that genetic mutations underlying brain development abnormalities and genes implicated in
neurodevelopmental psychiatric disorders can impact brain development in a variety of ways, but we currently
lack scalable tools for interrogating their impact on the development of specialized cell types.
 Astrocytes represent a highly diverse cell class that is broadly categorized into a handful of cardinal types.
Astrocytes emerge in late development, and selective vulnerabilities of astrocyte subtypes to mutations or
environmental perturbations may underlie distinct phenotypes in psychiatric disorders or in Zika virus infection.
However, developmental origins, molecular characteristics, and mechanisms of subtype specification are poorly
understood. We currently lack experimental methods to study human astrocyte subtypes and their development.
 Our preliminary data suggest that at mid-gestation, radial glia subtypes may be biased towards generating
different subtypes of human astrocytes. In the proposed project we propose to extend this finding by mapping
the temporal dynamics of cellular differentiation from radial glia subtypes across multiple stages of development.
We will also determine whether similar developmental dynamics take place in ferret, which could serve as a
substitute to human tissue and enable in vivo functional studies.
 Secondly, we will determine developmental lineage relationships between cortical radial glia subtypes and
astrocyte subtypes. Our preliminary studies predict morphologically distinct subtypes of astrocytes emerge from
anatomically distinct germinal niches, and we propose to directly register these morphotypes to transcriptomic
identities using single cell mRNA sequencing.
 Finally, our goal is to understand whether distinct radial glia subtypes contribute distinct cell types of the
cerebral cortex. To address this question, we propose to perform xenotransplantation experiments into mouse
brain. We will combine this approach with single cell sequencing, and in silico analyses co-embedding our data
with existing resources from adult human cortex to reveal what molecular subtypes may emerge from
transcriptomically- distinct subtypes of cortical progenitor cells.

## Key facts

- **NIH application ID:** 10841049
- **Project number:** 5R01NS123263-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Tomasz Nowakowski
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $421,489
- **Award type:** 5
- **Project period:** 2022-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841049

## Citation

> US National Institutes of Health, RePORTER application 10841049, Developmental Timing During Cortical Development (5R01NS123263-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10841049. Licensed CC0.

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