The role of SDHB in neural crest specification and migration

Abstract

Neural crest cells (NCCs) are a unique and crucial cell population in vertebrate embryonic development, contributing to the formation of diverse structures including the peripheral nervous system, craniofacial cartilage and bones, and the cardiac outflow tract. The role of cellular metabolism, particularly mitochondrial function, in NCC development remains poorly understood. This study investigated the specific role of Succinate Dehydrogenase subunit B (SDHB), a key component of mitochondrial complex II, in NCC development using a Wnt1Cre/+;Sdhbfl/fl;R26mTmG/mTmG mouse model. Through a combination of genetic manipulation, immunofluorescence analysis, and histological examination, we revealed that SDHB deletion in NCCs results in severe developmental defects, including profound craniofacial abnormalities, vascular defects, and neurological impairments. Our findings demonstrate a significant reduction in NCC migration and distribution, particularly in the cranial region. Moreover, we observed a dramatic increase in apoptosis of SDHB-deficient NCCs, with a rapid progression from partial to complete apoptosis of the neural crest population between embryonic days 10.5 and 11.5. Interestingly, we also noted altered proliferation dynamics in SDHB- deficient embryos, suggesting a complex interplay between increased apoptosis and dysregulated proliferation. These results highlight the critical importance of SDHB in NCC survival, migration, and di_erentiation throughout embryonic development. Our study provides novel insights into the metabolic regulation of NCC development and has important implications for understanding neurocristopathies and SDHB-related disorders, potentially opening new avenues for therapeutic interventions in these conditions.