Aberrant Gcm1 expression mediates Wnt/ß-catenin pathway activation in folate deficiency involved in neural tube defects.
Cell Death Dis
; 12(3): 234, 2021 03 04.
Article
em En
| MEDLINE
| ID: mdl-33664222
ABSTRACT
Wnt signaling plays a major role in early neural development. An aberrant activation in Wnt/ß-catenin pathway causes defective anteroposterior patterning, which results in neural tube closure defects (NTDs). Changes in folate metabolism may participate in early embryo fate determination. We have identified that folate deficiency activated Wnt/ß-catenin pathway by upregulating a chorion-specific transcription factor Gcm1. Specifically, folate deficiency promoted formation of the Gcm1/ß-catenin/T-cell factor (TCF4) complex formation to regulate the Wnt targeted gene transactivation through Wnt-responsive elements. Moreover, the transcription factor Nanog upregulated Gcm1 transcription in mESCs under folate deficiency. Lastly, in NTDs mouse models and low-folate NTDs human brain samples, Gcm1 and Wnt/ß-catenin targeted genes related to neural tube closure are specifically overexpressed. These results indicated that low-folate level promoted Wnt/ß-catenin signaling via activating Gcm1, and thus leaded into aberrant vertebrate neural development.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Proteínas de Ligação a DNA
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Tubo Neural
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Via de Sinalização Wnt
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Deficiência de Ácido Fólico
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Defeitos do Tubo Neural
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article