# Understanding the developmental progression of subpallial neural progenitor cells

> **NIH NIH R56** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $448,750

## Abstract

Project Summary
The embryonic ventral telencephalon, the subpallium, is the developmental origin of numerous brain structures
and cell populations such as the basal ganglia and cortical interneurons. These structures and cell populations
are critical for higher brain functions and are often causally involved in neuropsychiatric disorders such as
schizophrenia, autism, and drug addiction. Thus, a better understanding of ventral telencephalon development
will not only improve our understanding of brain development and brain function but also advance treatments
of nervous system disorders. All neurons and glia generated in the ventral telencephalon are descendants of
subpallial neural progenitor cells (NPCs), which here broadly include multipotent stem/progenitor cells known
as apical progenitors (APs) and lineage-restricted transit-amplifying cells known as basal or intermediate
progenitors (BPs). Because research on NPCs during mammalian brain development has focused on the
cortex, comparatively little is known about the steps of the developmental progression of subpallial NPCs and
the mechanisms involved, although it is evident that subpallial NPCs must possess unique features that
underlie their distinct cellular outputs (in terms of cell number and cell type). The objective of this application is
to investigate the cellular and molecular mechanisms that control the developmental progression of subpallial
NPCs. Recently, by analyzing a conditional knockout mouse line lacking Tead1 and Tead2, which encode key
transcription factors of the Hippo pathway—a signaling pathway crucial for the development, tumorigenesis,
and regeneration of most tissues across species, we found that the TEAD transcription factors are novel
regulators of the developmental progression of subpallial NPCs; they uniquely regulate subpallial, but not
pallial (cortical), NPCs and act through Hippo pathway-dependent and -independent mechanisms. The central
hypothesis of this proposal is that TEAD regulates the developmental progression of subpallial NPCs with a
dual mode of action: in APs, TEAD interacts with YAP/TAZ to maintain the AP state; in BPs, however, TEAD
interacts with INSM1 to repress the AP state and promote developmental progression. Specifically, the
proposed study will: (1) dissect the role of TEAD in ventral telencephalon development by using various
genetic modified mouse models, (2) determine whether TEAD acts through INSM1 in subpallial basal
progenitors, and (3) define the transcriptional mechanism through which TEAD regulates subpallial NPCs. The
proposed study is expected to expand our knowledge of the mechanisms that uniquely regulate the
developmental progression of subpallial NPCs and improve our understanding of an important signaling
pathway—the Hippo pathway.

## Key facts

- **NIH application ID:** 10263447
- **Project number:** 1R56NS119760-01
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Xinwei Cao
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $448,750
- **Award type:** 1
- **Project period:** 2020-09-30 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10263447

## Citation

> US National Institutes of Health, RePORTER application 10263447, Understanding the developmental progression of subpallial neural progenitor cells (1R56NS119760-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10263447. Licensed CC0.

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