A missense mutation in the C. elegans src-2 tyrosine-protein kinase reduces brood size and enhances embryonic morphogenesis defects in src-1(RNAi) conditions
Year: 2023
Type: article
Abstract: Goldenhar Syndrome is a rare congenital disorder characterized by hemifacial microsomia. Although select mutations have been mapped for this disorder, the genetic etiologies in the majority of cases remain unknown. A recent clinical report of a Goldenhar Syndrome patient identified a homozygous missense mutation in FRK, a gene associated with various types of cancer. In this work, we precisely modeled the disease-associated missense mutation in the C. elegans FRK ortholog src-2, using CRISPR/Cas9 gene editing, and investigated the physiological role of this mutation and the src-2 gene. In addition, we generated a conserved variant in src-1 (FYN ortholog) to assess the functional redundancy of the conserved variant. The putative pathogenic variants src-1(Val190Ile) or src-2(Val170Ile) caused only subtle phenotypes, suggesting that these mutations alone are not sufficient to explain the facial deformities observed in the Goldenhar Syndrome patient. However, the src-2(Val170Ile) mutant exhibited reduced brood size and moderately enhanced embryonic developmental phenotypes, including epidermal and neuronal patterning defects, in the src-1(RNAi) condition, indicating that the src-2(Val170Ile) locus could play a supportive role during developmental processes. Overall, however, these studies showed that src-1/FYN is essential for regulating embryogenesis and morphogenesis, while src-2/FRK is largely dispensable for normal embryonic development, suggesting FYN, not FRK, is the dominant non-receptor protein kinase during embryonic development in C. elegans.
Source: PubMed Central
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4385295312