Page 149 - CSIR-IGIB Annual Report 2020-21
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Tracing melanocyte migration to external cues appear to have a diffused expression pattern that
Colors and patterns are amongst the most widely cannot give directionality per se. The chemotaxis
used descriptive adjectives to distinctly identify assays conducted on B16 melanocytes in a
individuals. In biological systems, colors are competitive chemotactic environment (repulsive
produced by a specialized cell type referred to as Sema3E versus chemokinetic SCF) illustrated that
chromatophores. Numbers, type and positioning Sema3e availability introduces directionality in the
of these chromatophores manifest in the form of chemokinetic behaviour of B16 melanocytes in
beautiful pigment pattern(s) conserved across presence of SCF.
animal species. However, during the extensive
course of vertebrate evolution both the number Tracing the origin of proofreading in SARS-Cov2
and types of chromatophores have narrowed Unusually large genome size in coronaviruses is
down, subsequently leading to more uniform coat attributed to replication fidelity conferred by
colors. We have been addressing mechanisms proof-reading exonuclease (ExoN). This enzyme
behind that establishment of melanocyte functions alongside RNA replicase and has
guidance modality that stands conserved across emerged as a solution to Eigen’s paradox on
vertebrates. Our experiments in zebrafish embryo replication fidelity and genome size threshold.
reveal that migrating melanocytes express Evolutionary history of coronaviruses holds the
Semaphorin receptor plexinD1(plxnd1) that key to understand mutational behavior and
regulates melanoblast positioning along the prepare for possible future outbreaks. In this
lateral mid-line and fine-tunes their ErbB signaling study, by performing comparative genome
response. Loss of plxnd1 mediated guidance leads analysis of nidovirales that contain the family of
to inefficient streaming of melanoblasts in ventral coronaviruses, we traced the origin of ExoN,
routes therefore depriving them of ErbB signaling. surprisingly to the eukaryotic antiviral component
Adult melanocyte stem cell establishment in ZNFX1. This common recent ancestral protein
plxnd1 morphants therefore is insufficient, which contributes two zinc finger (ZnF) motifs that are
accounts for their inability to regenerate unique to viral exonuclease, segregating them
melanocytes upon chemical ablation by MoTP. from DNA proof-readers. Phylogenetic analyses
The medio-lateral spreading of melanoblasts and indicated that following acquisition, genomes of
their subsequent proliferation and differentiation coronaviruses retained and further fine-tuned
is dependent on cKIT signaling. Kit ligand (kitla) or ExoN, whereas related families harbor
Stem Cell Factor (SCF) is expressed all along the substitution of key residues in ZnF1 motif
pre-somitic mesoderm of the tail bud (posterior concomitant to a reduction in their genome sizes.
end). This facilitates migration and differentiation Structural modelling followed by simulation
of melanoblast along the lateral body towards the studies suggested the role of ZnF in RNA binding.
tail. A group of cells at the horizontal myoseptum Key ZnF residues strongly coevolve with replicase,
in the middle of each somite in the trunk beginning and the helicase involved in duplex RNA
at 22hpf through 30hpf express kitla. This unwinding, reiterating role of ExoN in mismatch
expression timeline perfectly coincides with recognition for repair. Hence, fidelity of
melanocyte precursor migration in ventro-medial replication among coronaviruses is a result of
streams. The positive regulators of melanoblast convergent evolution, that enables maintenance
migration (ET1/SCF/α-MSH) act by chemokinesis. of genome stability akin to cellular proofreading
These identified migration promoting chemokines systems.
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