A new mib allele with a chromosomal deletion covering foxc1a exhibits anterior somite specification defect

Abstract

mibnn2002, found from an allele screen, showed early segmentation defect and severe cell death phenotypes, which are different from previously known mib mutants. Despite distinct morphological phenotypes, the typical mib molecular phenotypes: her4 down-regulation, neurogenic phenotype and cold sensitive dlc expression pattern, still remained. The linkage analysis also indicated that mibnn2002 is a new mib allele. Failure of specification in anterior 7-10 somites is likely due to lack of foxc1a expression in mibnn2002 homozygotes. Somites and somite markers gradually appeared after 7-10 somite stage, suggesting that foxc1a is only essential for the formation of anterior 7-10 somites. Apoptosis began around 16-somite stage with p53 up-regulation. To find the possible links of mib, foxc1a and apoptosis, transcriptome analysis was employed. About 140 genes, including wnt3a, foxc1a and mib, were not detected in the homozygotes. Overexpression of foxc1a mRNA in mibnn2002 homozygotes partially rescued the anterior somite specification. In the process of characterizing mibnn2002 mutation, we integrated the scaffolds containing mib locus into chromosome 2 (or linkage group 2, LG2) based on synteny comparison and transcriptome results. Genomic PCR analysis further supported the conclusion and showed that mibnn2002 has a chromosomal deletion with the size of about 9.6 Mbp.

foxc1aandfoxc1bdifferentially regulate angiogenesis from arteries and veins by modulating Vascular Endothelial Growth Factor signalling

“…S4B arrowheads), the formation of somites 1-4 was abnormal in foxc1a mutants ( Fig. S4A, C, E, F red arrowheads, G) consistent with previous reports (Hsu et al, 2015;Li et al, 2015). In addition, foxc1a mutants displayed a significant increase in somitic angle of posterior somites ( Fig S4E, F, H), which likely accounts for straightened ISVs in these mutants.…”

“…In addition, knockdown of foxc1a/b in zebrafish has been reported to reduce Etv2 promoter activity, suggesting these genes also function upstream of Etv2 (Veldman and Lin, 2012). Several recent studies using foxc1a mutants have indicated a requirement for foxc1a during neural circuit development (Banerjee et al, 2015) in addition to anterior somite formation (Hsu et al, 2015;Li et al, 2015) which is consistent with previous knockdown studies (Topczewska et al, 2001b).…”

“…Previous studies have demonstrated functions for foxc1a during somite formation and patterning (Hsu et al, 2015;Li et al, 2015;Topczewska et al, 2001b) and abnormal somite formation is known to influence the migratory path of ECs (Shaw et al, 2006). We therefore examined somite morphology in our foxc1 mutants and identified that while somite morphology was normal in foxc1b mutants consistent with normal ISV patterning in these ( Fig.…”

Identification of a new adtrp1‐tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis

“…6A-D). A similar analysis revealed no obvious difference for elavl3, a nervous system marker for the differentiation of the ectoderm (33), between adtrp1 morphants and control embryos that were injected with Std-MO (Supplemental Fig. 6E, F).…”

foxc1agenetically interacts withripply1to regulatemesp-baexpression and somitogenesis in the zebrafish embryo

“…Accumulating evidence in recent years suggests that Foxc1 has an important, dose dependent role in somite formation and axial skeletal development [20,[22][23][24]. Mice with null Foxc1 mutations have defects in axial skeletal development, such as incomplete formation of the neural arches, misshapen ribs, and fused vertebrae, along with cardiovascular, ocular and other anomalies [20].…”