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Investigating the role of brinp1 in zebrafish development
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posted on 22.02.2017by Giousoh, Aminah
The Membrane Attack Complex - PerForin (MACPF) superfamily is known to have a
diverse array of roles in immunity, embryonic development and neural function. BRINPs (Bone
Morphogenetic Protein – Retinoic Acid Inducible Neural specific Proteins) are a family of three
MACPF domain-containing proteins that are highly expressed during rodent neural
development. Each contains a MACPF domain, but the remainder of the molecule has no
significant sequence similarity to any other structurally or functionally characterised protein.
BRINP orthologues are highly conserved across vertebrates, suggesting they perform essential
functions. In rodents, all three Brinps are ubiquitously expressed in the brain at early embryonic
stages, with Brinp1 most highly expressed. In postnatal to adult stages Brinp1 expression is
restricted to the hippocampus, olfactory bulb, cerebellum and cerebral cortex. Only low
expression of Brinp2 and Brinp3 is observed at these stages.
In this study, the zebrafish animal model was used to study the function of brinps in the
developing brain, and to determine the effect of disrupting their function. A bioinformatic
approach was applied to explore the evolutionary relationships between BRINP family members.
The locus arrangement of BRINP genes is conserved in mammals and teleosts. Full-length
zebrafish orthologues were identified and cloned, and two additional brinp3 paralogues were
discovered. Brinp gene expression in zebrafish was reminiscent of the expression in rodents.
Expression was unrestricted in the brain at early stages (24 hpf) and localised to specific brain
structures in older embryos (48-72 hpf). Expression was also observed in the primordial fin
buds. In addition to the broad and overlapping expression pattern of all brinps, brinp1 was
exclusively detected in the lateral line primordium.
Through morpholino oligonucleotide gene silencing, loss of function of the brinp1 gene
was examined and determined to result in pleiotropic defects in the developing embryo. At 48
hpf, embryos exhibited a curved body axis, aberrant neuromast formation and defects in axonal
projections in the head and tail. Finally, this study has led to the identification of a pathway in
which brinp1 may function. It was possible to reverse the effect of the curved tail and loss of
neuromasts by 72 hpf using a Tyrosine kinase B (TrkB) receptor agonist, providing preliminary
evidence that brinp1 functions in the BDNF/ TrkB receptor pathway.