# Genomic recording systems to reveal evolutionary modifications in primate neocortex

> **NIH NIH DP2** · PRINCETON UNIVERSITY · 2024 · $1,389,728

## Abstract

Project Summary/Abstract
Primate brains develop following an exquisitely conserved Bauplan that is shared with other mammals, yet also
possess advanced cognitive capabilities. These capabilities manifest from innovations to cellular and molecular
repertoires, but the developmental origin of these evolutionary modifications has remained elusive due to lack
of tools that enable access to primate neurodevelopmental processes. A major evolutionary modification is the
expansion of the neocortex. Within the neocortex, areas associated with higher-order cognitive functions (and
their disorders) have expanded disproportionately relative to areas that process sensory information. The
increase in cortical territory devoted to higher-order processing has been accompanied by fundamental
differences in neocortical cell type composition (the absolute and relative proportions of different cell types),
gene expression, and cell-cell connectivity properties. For example, unlike sensory areas, higher-order areas
are typified by long-range connectivity to other higher-order areas. Mechanisms for the establishment of
primary sensory areas and their connectivity have been worked out in mice, but it is not known whether these
rules are conserved in primates, especially in expanded higher-order neocortex which lacks a rodent homolog.
Thus, we lack understanding of when and why higher-order areas establish their unique cellular characteristics
and come to disproportionately connect to each other to form the long-range networks in primate brains. This
proposal seeks to address this gap by applying modern molecular tools and genomic analyses to discover
rules for the development and connectivity of sensory and higher order areas in the common marmoset, an
emerging and genetically tractable primate model species. Cellular lineage tracing methods delivered in utero
to developing marmosets will be paired with single cell RNA and DNA sequencing to reconstruct lineage
relationships and progenitor population demographics across sensory and higher order areas. Lineage-
resolved spatial sequencing will determine how clonal dispersion statistics differ between primary sensory and
higher-order areas, and between marmosets and mice. Emerging technologies for reconstructing the
connections between individual cells, such as those based on barcoded, synapse-transiting viruses, will reveal
how and when connectivity is established across brain areas. Marmosets offer distinct advantages for this
program, including a high-quality genome, small size, and rapid sexual maturity, while retaining primate-
specific brain features such as expanded higher-order cortex and long-range connectivity. This research
program leverages the power of quantitative genomic measurement and cell type-resolved recording
technologies to reconstruct the developmental and evolutionary histories of primate brain specializations. The
knowledge and expertise gained by developing this expanded toolbox will improve acce...

## Key facts

- **NIH application ID:** 10910556
- **Project number:** 1DP2MH140136-01
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Fenna Marie Krienen
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,389,728
- **Award type:** 1
- **Project period:** 2024-09-15 → 2027-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910556

## Citation

> US National Institutes of Health, RePORTER application 10910556, Genomic recording systems to reveal evolutionary modifications in primate neocortex (1DP2MH140136-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10910556. Licensed CC0.

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