# Unraveling the essential gene regulatory network underlying notochord development in Ciona

> **NIH NIH R03** · NEW YORK UNIVERSITY · 2020 · $79,250

## Abstract

PROJECT SUMMARY/ABSTRACT
 In humans and all chordates the notochord plays an indispensable role in supporting and patterning the
developing body plan. During embryogenesis, defects in notochord formation are the cause of birth defects
such as spina bifida and vertebral deformities, while during post-natal development notochord remnants can
cause painful discopathy and, more rarely, chordomas, malignant and potentially life-threatening tumors.
Despite the considerable biomedical interest in the role of the notochord in spine development and in
tumorigenesis, both the comprehension of the specific functions of evolutionarily conserved transcription
factors in notochord development and the knowledge of the cis-regulatory mechanisms controlling notochord
gene expression are still fragmentary. These gaps in knowledge greatly limit our ability to pinpoint the genes
and regulatory sequences responsible for notochord-derived defects and to potentially rectify their expression.
We use the invertebrate chordate Ciona (tunicate, or sea squirt) to investigate the role of evolutionarily
conserved transcription factors in notochord formation and to uncover the regulatory mechanisms that ensure
their proper deployment during the development of this crucial structure. Ciona was selected for these studies
because it provides a fast-developing model system with an experimentally accessible notochord and a
compact, fully sequenced genome, and because several genes expressed in the Ciona notochord are
evolutionarily conserved across all chordates. The objective of this project is to establish in our laboratory the
CRISPR/Cas9-mediated genome editing technique for systematically knocking down notochord transcription
factors of interest and for editing their regulatory regions and determine the effects on gene expression. These
resources will advance our research on the evolutionarily conserved genetic toolkit that is employed by widely
different chordates to properly form the notochord and guide the correct formation of the body plan.
The objective of this proposal will be obtained through the following approaches: the identification of the cis-
regulatory modules (CRMs) that control notochord gene expression of 10 evolutionarily conserved transcription
factors (Aim 1); the elucidation of the function of these transcription factors in specific steps of notochord
morphogenesis (Aim 2). Completion of these experiments will shed light on the components of the notochord
GRN and their reciprocal regulatory interactions and will inform and accelerate studies of notochord-derived
birth defects in other chordates.

## Key facts

- **NIH application ID:** 9884798
- **Project number:** 5R03HD098395-02
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** ANNA DI GREGORIO
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $79,250
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9884798

## Citation

> US National Institutes of Health, RePORTER application 9884798, Unraveling the essential gene regulatory network underlying notochord development in Ciona (5R03HD098395-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9884798. Licensed CC0.

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