# The reverse hingepoint: a novel, essential feature of neurulation

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE COUNTY · 2021 · $225,938

## Abstract

Abstract
Neural tube defects (NTDs) are the second most common structural birth defect, yet despite their high
frequency, the fundamental mechanisms that shape the neural tube are still poorly understood. During
neurulation, the neural plate bends and folds in a biphasic manner around a medial and bi-lateral
hingepoints, bringing the neural folds in close apposition and leading to their fusion, which completes
neural tube formation. The discovery of the medial hingepoint was pivotal to the field, as it not only
provided a mechanistic explanation for how the flat neural plate initially bends into a V shape, but it
also led to the identification of several causative mutations in patients with NTDs. In contrast to the
central region of the neural plate, the edges of this epithelial layer fold in the opposite direction to
shape the neural folds. It stands to reason that this process would involve a reverse change in cell
shape (reverse hingepoint or RHP) and preliminary data confirms this prediction, however a molecular
understand of this process is lacking. We propose to test the central hypothesis that RHP formation
is driven by recruitment of contractile machinery to the basal pole of neural fold cells, downstream of
spatial information conveyed by forebrain-specific transcription factors. In aim 1 we will investigate the
molecular mechanisms that shape RHP cells and in aim 2 we will examine how regional identity
conveyed by forebrain-specific transcription factors species where RHPs form.
Upon completion of the proposed studies, we will understand key cellular and molecular mechanisms
that mediate RHP formation and have filled an important gap in our basic knowledge of neurulation.
These studies will pave the way towards identification of novel NTD genetic risk factors by providing a
developmental framework for functional validation of human variants in candidate genes such as
emx2 and integrin b1.

## Key facts

- **NIH application ID:** 10217527
- **Project number:** 1R21HD102630-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE COUNTY
- **Principal Investigator:** Rachel Melissa Brewster
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $225,938
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217527

## Citation

> US National Institutes of Health, RePORTER application 10217527, The reverse hingepoint: a novel, essential feature of neurulation (1R21HD102630-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10217527. Licensed CC0.

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