# The developmental origins and fate of neurons in the gyrencephalic neocortex

> **NIH NIH R21** · CHILDREN'S RESEARCH INSTITUTE · 2022 · $267,750

## Abstract

SUMMARY/ABSTRACT:
Diverse networks of neurons and glia produce the advanced computational power of the mammalian brain.
Neural precursor cell (NPC) populations present in the ventricular and subventricular zones (VZ and SVZ) of the
prenatal brain generate all neurons and glia either directly, or indirectly via intermediate progenitors. While there
has been a rapid increase in understanding the cell diversity and underlying genetic mechanisms of these
precursor cells, most of this work has been accomplished in the lissencephalic rodent. Some recent findings in
gyrencephalic species indicate that NPC types and their developmental mechanisms are tuned differently in
species with larger brains. For example, recent studies have discovered that, unlike in rodents, the density of
basal radial glial cells (bRGCs) is significantly higher in primate brain, but the neuroanatomical and
neurophysiological advantage(s) of this difference have not been established. Similarly, large numbers of
neurons migrating to the frontal lobe are present in the human infant brain but are not found in mouse; neither
the mechanisms underlying their prenatal generation nor their processes of integration into the neocortex have
been identified. While single cell transcriptomic data has opened new windows into the gene expression
underlying this diversity, the ability to not only confirm species-specific differences but to also interrogate their
effects in vivo is hampered by the lack of an appropriate model. Piglets are a powerful model with which to study
complex brain development because they have a highly evolved gyrencephalic neocortex. Our previous studies
found that the cytoarchitecture of the porcine SVZ is exceptionally similar to its human counterpart. Consistent
with the human infant cortex, young neurons in the piglet SVZ migrate to the frontal cortex and differentiate into
neurons in a region-specific manner. Finally, our recent collaborative single cell sequencing study has uncovered
cell populations with unique molecular profiles within the piglet SVZ that are not found in rodent SVZ. Thus, we
hypothesize that elucidating the diversity and fate potential of the porcine VZ and SVZ neural precursors will
accelerate our understanding of human neuronal diversity, cortical circuit complexity and cognitive ability. Our
project will establish an in vivo gene delivery method to visualize NPC dynamics and neuronal specification in
the fetal piglet VZ and SVZ (Aim 1); and visualize late-migrating neurons and cell populations derived from the
postnatal piglet SVZ (Aim 2). Establishment of a system in which a large gyrencephalic brain can be studied
using modern genetic and cellular imaging techniques would significantly impact our understanding of normal
human brain development and provide a critical tool for elucidating the etiology for neurodevelopmental
disorders. This advance will enable key comparative studies with other datasets from gyrencephalic and
lissencephalic sp...

## Key facts

- **NIH application ID:** 10429019
- **Project number:** 1R21NS127051-01
- **Recipient organization:** CHILDREN'S RESEARCH INSTITUTE
- **Principal Investigator:** Tarik F Haydar
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $267,750
- **Award type:** 1
- **Project period:** 2022-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10429019

## Citation

> US National Institutes of Health, RePORTER application 10429019, The developmental origins and fate of neurons in the gyrencephalic neocortex (1R21NS127051-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10429019. Licensed CC0.

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