# Single-cell transcriptomics reveals the cellular identity of a novel progenitor population crucial for murine neural tube closure

## TL;DR

Single-cell analysis identifies a new progenitor cell population critical for mouse neural tube closure and spina bifida prevention.

## Contribution

Discovery of a novel progenitor population defined by co-expression of Grhl3, Tfap2a, and Tfap2c essential for neural tube closure.

## Key findings

- Co-expression of Grhl3, Tfap2a, and Tfap2c defines a novel progenitor population in surface ectoderm crucial for neural tube closure.
- Deletion of Grhl3 in this population or Tfap2c in Grhl3-expressing cells causes spina bifida in mice.
- Findings highlight the importance of a specific neural plate border cell cohort in early neurulation.

## Abstract

Neural tube closure in vertebrates is achieved through a highly dynamic and coordinated series of morphogenic events involving neuroepithelium, surface ectoderm, and neural plate border. Failure of this process in the caudal region causes spina bifida. Grainyhead-like 3 (GRHL3) is an indispensable transcription factor for neural tube closure as constitutive inactivation of the Grhl3 gene in mice leads to fully penetrant spina bifida. Here, through single-cell transcriptomics we show that at E8.5, the time-point preceding mouse neural tube closure, co-expression of Grhl3, Tfap2a, and Tfap2c defines a previously unrecognised progenitor population of surface ectoderm integral for neural tube closure. Deletion of Grhl3 expression in this cell population using a Tfap2a-Cre transgene recapitulates the spina bifida observed in Grhl3-null animals. Moreover, conditional inactivation of Tfap2c expression in Grhl3-expressing neural plate border cells also induces spina bifida. These findings indicate that a specific neural plate border cellular cohort is required for the early-stage neurulation.

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