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EMG1 cooperates with GRHL3 in β-catenin–mediated surface ectoderm differentiation to regulate neural tube closure

ABSTRACT: Grainyhead-like transcription factor 3 (GRHL3) directs surface ectoderm differentiation under the control of the canonical Wnt/β-catenin pathway. However, the molecular mechanisms that control nuclear GRHL3 expression through β-catenin are not fully understood. Here, we show that the essential for mitotic growth 1 (EMG1) protein constitutes a protein complex with GRHL3, and that EMG1 is required for correct nuclear localization of GRHL3, and for activation of the canonical Wnt signaling pathway. Conditional knockout mutation of Emg1 in the GRHL3-positive surface ectoderm causes neural tube defects at the level of the spinal cord, i.e. spina bifida. Additionally, the severity of compound mutant phenotypes of the Emg1 and Grhl3 genes indicates that they interact genetically in neurulation and palate development. These lines of evidence demonstrate that EMG1 cooperates with GRHL3 in β-catenin–mediated surface ectoderm differentiation. Since the EMG1 mutation causes Bowen-Conradi syndrome and the GRHL3 mutation causes Van der Woude syndrome 2, both of which are associated with neural tube dysplasia and cleft palate, our study will help to better understand the pathogenic mechanisms of these two human genetic diseases.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Chiharu Kimura-Yoshida, Isao Matsuo

PROVIDER: PXD056807 | JPOST Repository | Tue Jul 01 00:00:00 BST 2025

REPOSITORIES: jPOST

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			Action	DRS
	20240501_QE1_HTCPAL_sand_AcOH_PE_SUSValve_2024_057_Alignment_Norm.mzTab	Mztab
	20240501_QE1_HTCPAL_sand_AcOH_PE_SUSValve_2024_057_Alignment_Norm.mzid	Mzid
	20240501_QE1_HTCPAL_sand_AcOH_PE_SUSValve_2024_057_Alignment_Norm_All_Proteins.xlsx	Xlsx
	20240501_QE1_HTCPAL_sand_AcOH_PE_SUSValve_2024_057_e1.raw	Raw
	20240501_QE1_HTCPAL_sand_AcOH_PE_SUSValve_2024_057_e2.raw	Raw

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EMG1 cooperates with GRHL3 in β-catenin–mediated surface ectoderm differentiation to regulate neural tube closure

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