Eif3ba regulates cranial neural crest development by modulating p53 in zebrafish

Abstract

Congenital diseases caused by abnormal development of the cranial neural crest usually present craniofacial malformations and heart defects while the precise mechanism is not fully understood. Here, we show that the zebrafish eif3ba mutant caused by pseudo-typed retrovirus insertion exhibited a similar phenotype due to the hypogenesis of cranial neural crest cells (NCCs). The derivatives of cranial NCCs, including the NCC-derived cell population of pharyngeal arches, craniofacial cartilage, pigment cells and the myocardium derived from cardiac NCCs, were affected in this mutant. The expression of several neural crest marker genes, including crestin, dlx2a and nrp2b, was specifically reduced in the cranial regions of the eif3ba mutant. Through fluorescence-tracing of the cranial NCC migration marker nrp2b, we observed reduced intensity of NCC-derived cells in the heart. In addition, p53 was markedly up-regulated in the eif3ba mutant embryos, which correlated with pronounced apoptosis in the cranial area as shown by TUNEL staining. These findings suggest a novel function of eif3ba during embryonic development and a novel level of regulation in the process of cranial NCC development, in addition to providing a potential animal model to mimic congenital diseases due to cranial NCC defects. Furthermore, we report the identification of a novel transgenic fish line Et(gata2a:EGFP)pku418 to trace the migration of cranial NCCs (including cardiac NCCs); this may serve as an invaluable tool for investigating the development and dynamics of cranial NCCs during zebrafish embryogenesis.

Two developmentally distinct populations of neural crest cells contribute to the zebrafish heart

“…In addition, mCherry positive NC-derived cells were detected in the developing heart (Figs. 2, 3), confirming previous reports that some NC-derived cells contribute to the zebrafish heart (Li et al, 2003; Sato and Yost, 2003; Kague et al, 2012; Mongera et al, 2013; Xia et al, 2013). …”

Variable developmental delays and characteristic facial features—A novel 7p22.3p22.2 microdeletion syndrome?

“…EIF3B encodes a subunit of the eukaryotic translation initiation factor 3 (eIF3), which is a complex that plays an important role in initiation of translation (El Antak, Tzakos, Locker, & Lukavsky, ). Anatomical abnormalities are not described in Eif3b +/− mice (Koyanagi‐Katsuta et al, ) or in zebrafish which are heterozygous for mutations in eif3ba (Xia et al, ). Zebrafish which are homozygous for mutations in eif3ba manifest malformations of the head and heart defects which suggests that the gene has a role in the development of neural crest cells (Xia et al, ).…”

“…Anatomical abnormalities are not described in Eif3b +/− mice (Koyanagi‐Katsuta et al, ) or in zebrafish which are heterozygous for mutations in eif3ba (Xia et al, ). Zebrafish which are homozygous for mutations in eif3ba manifest malformations of the head and heart defects which suggests that the gene has a role in the development of neural crest cells (Xia et al, ). However, the role of EIF3B in human development is not yet known.…”

Neural crest delamination and migration: Looking forward to the next 150 years

“…Aquatic species are exposed to large variations of oxygen concentrations in their local environment and Hif1α expression is probably controlled by additional mechanisms to ensure developmental robustness. Interestingly, increased p53 expression in the eif3ba zebrafish mutant is associated with an increased apoptosis and a dramatic reduction of cranial NC cells (Xia et al, ). This raises the possibility of an interplay between p53 and Hif1α .…”