Key result
Neural crest Mrpl40 deletion causes conotruncal defects and impairs cell migration via CREB-Msx1 disruption.
Why the study?
The functions of most genes within the deleted 22q11.2 region in heart development remain poorly understood, including the role of Mrpl40 in cardiac morphogenesis.
Deletion of the mitochondrial ribosomal gene Mrpl40 in neural crest cells impairs their migration via disrupted CREB-MSX1 signaling, leading to delayed cardiac outflow tract septation and conotruncal defects relevant to 22q11.2 deletion syndrome.
Answers are grounded in this paper and cite their sources.
Mrpl40 haploinsufficiency may contribute to septal defects in 22q11.2DS models; leaves open complex mitochondrial gene interactions for mechanistic studies.
22q11.2 deletion syndrome (22q11.2DS) causes multi-system disorders, among which congenital heart defects are predominant, typically manifesting as conotruncal anomalies. Within the deleted 22q11.2 region, several genes have been identified as critical regulators of heart development; however, the functions of most genes in this interval remain poorly understood. Here, we investigated Mrpl40 , which encodes the mitochondrial ribosomal protein L40 (MRPL40), to determine its function in cardiac morphogenesis. Deletion of Mrpl40 in neural crest cells (NCCs) resulted in conotruncal defects. Specifically, Mrpl40 deficiency impaired NCC migration, leading to delayed outflow tract (OFT) septation and aberrant rotation. Mechanistically, we found that Mrpl40 loss disrupted CREB phosphorylation, resulting in reduced expression of Msx1 , a crucial regulator of NCC migration and differentiation. Collectively, this study demonstrates the pivotal function of mitochondria in NCC behavior and defines the essential role of Mrpl40 in OFT development, and provides new insights to understand the etiology of 22q11.2DS.
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Ji et al. (2026) studied 22q11.2 deletion syndrome (22q11.2DS) / Conotruncal congenital heart defects. Deletion of Mrpl40 in neural crest cells was evaluated on Conotruncal defects, outflow tract septation, and neural crest cell migration. Deletion of Mrpl40 in neural crest cells impaired cell migration and caused conotruncal defects and delayed outflow tract septation by disrupting CREB phosphorylation and reducing Msx1 expression.
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