Loss of protein C vs protein S results in discrepant thrombotic phenotypes.

Venous thrombosis is a leading cause of morbidity/mortality and associated with deficiencies of the anticoagulant protein C (PC, PROC) and its cofactor, protein S (PS, PROS1). Heterozygous mutations increase the risk of adult-onset thrombosis, while homozygous mutations result in pre/neonatal lethal thrombosis. PC- and PS-deficient patient phenotypes are generally considered clinically indistinguishable.

A genetic modifier of venous thrombosis in zebrafish reveals a functional role for fibrinogen AαE in early hemostasis.

Plasma fibrinogen molecules comprise 2 copies of Aα, Bβ, and γ chains folded into a hexameric protein. A minor fibrinogen isoform with an extended Aα chain (AαE) is more abundant in newborn human blood than in adults. Larval zebrafish produce predominantly AαE-containing fibrinogen, but its functional significance is unclear.

Zebrafish otolith biomineralization requires polyketide synthase.

Deflecting biomineralized crystals attached to vestibular hair cells are necessary for maintaining balance. Zebrafish (Danio rerio) are useful organisms to study these biomineralized crystals called otoliths, as many required genes are homologous to human otoconial development. We sought to identify and characterize the causative gene in a trio of homozygous recessive mutants, no content (nco) and corkscrew (csr), and vanished (vns), which fail to develop otoliths during early ear development.

Autophagy regulates cytoplasmic remodeling during cell reprogramming in a zebrafish model of muscle regeneration.

Cell identity involves both selective gene activity and specialization of cytoplasmic architecture and protein machinery. Similarly, reprogramming differentiated cells requires both genetic program alterations and remodeling of the cellular architecture. While changes in genetic and epigenetic programs have been well documented in dedifferentiating cells, the pathways responsible for remodeling the cellular architecture and eliminating specialized protein complexes are not as well understood.

Myocyte Dedifferentiation Drives Extraocular Muscle Regeneration in Adult Zebrafish.

Purpose: The purpose of this study was to characterize the injury response of extraocular muscles (EOMs) in adult zebrafish.

Methods: Adult zebrafish underwent lateral rectus (LR) muscle myectomy surgery to remove 50% of the muscle, followed by molecular and cellular characterization of the tissue response to the injury.

Results: Following myectomy, the LR muscle regenerated an anatomically correct and functional muscle within 7 to 10 days post injury (DPI).

Natural variability of Kozak sequences correlates with function in a zebrafish model.

In eukaryotes, targeting the small ribosomal subunit to the mRNA transcript requires a Kozak sequence at the translation initiation site. Despite the critical importance of the Kozak sequence to regulation of gene expression, there have been no correlation studies between its natural variance and efficiency of translation. Combining bioinformatics analysis with molecular biology techniques, and using zebrafish as a test case, we identify Kozak sequences based on their natural variance and characterize their function in vivo.