Biology subjects

Truong, V. H.

Publications and source records attributed to Truong, V. H..

3 recordsLinked to original sources

bioRxiv2025

Choroid Plexus Hosts the Earliest Detectable Circadian Clock in the Brain

Maternal chronodisruption is linked to miscarriages and neurodevelopmental risks, yet the earliest brain circadian oscillator in the embryo and the mechanism of its emergence remain unknown. Using bioluminescent reporters for PER2 and Bmal1, we tracked the onset of autonomous [~]24 h oscillations ex vivo. While the suprachiasmatic nucleus (SCN) is widely considered the first circadian structure at embryonic day (E) 14.5-15.5, we find that the fourth ventricle choroid plexus (4VCP) exhibits PER2 oscillations by E11.5-E12.5. These oscillations show hallmarks of a saddle-node on an invariant circle (SNIC) bifurcation, characterized by an initially long period converging toward 24 h and pronounced sensitivity to sub-degree temperature cycles mimicking physiological maternal cues. Transcriptional profiling of maternal and embryonic 4VCPs unveiled three epochs in clock gene expression that parallel tissue differentiation. We identify the 4VCP as the earliest detectable brain circadian oscillator, and demonstrate how its bifurcation dynamics allow the nascent clock to couple to maternal rhythms.

developmental biology↗

bioRxiv2024

Gag proteins encoded by endogenous retroviruses are required for zebrafish development

Transposable elements (TEs) make up the bulk of eukaryotic genomes and examples abound of TE-derived sequences repurposed for organismal function. The process by which TEs become coopted remains obscure because most cases involve ancient, transpositionally inactive elements. Reports of active TEs serving beneficial functions are scarce and often contentious due to difficulties in manipulating repetitive sequences. Here we show that recently active TEs in zebrafish encode products critical for embryonic development. Knockdown and rescue experiments demonstrate that the endogenous retrovirus family BHIKHARI-1 (Bik-1) encodes a Gag protein essential for mesoderm development. Mechanistically, Bik-1 Gag associates with the cell membrane and its ectopic expression in chicken embryos alters cell migration. Similarly, depletion of BHIKHARI-2 Gag, a relative of Bik-1, causes defects in neural crest development in zebrafish. We propose an "addiction" model to explain how active TEs can be integrated into conserved developmental processes.

developmental biology↗

bioRxiv2022

Structures of the holo CRISPR RNA-guided transposon integration complex

CRISPR-associated transposons (CAST) are programmable mobile elements that insert large DNA cargo by an RNA-guided mechanism. Multiple conserved components act in concert at the target site through formation of an integration complex (transpososome). We reconstituted the type V-K CAST transpososome from Scytonema hofmannii (ShCAST) and determined the structure using cryo-EM. Transpososome architecture ensures orientation-specific association: AAA+ regulator TnsC has defined polarity and length, with dedicated interaction interfaces for other CAST components. Interestingly, transposase (TnsB)-TnsC interactions we observe contribute to stimulating TnsCs ATP hydrolysis activity. TnsC deviates from previously observed helical configurations of TnsC, and target DNA does not track with TnsC protomers. Consequently, TnsC makes new, functionally important protein-DNA interactions throughout the transpososome. Finally, two distinct transpososome populations suggests that associations with the CRISPR effector are flexible. These ShCAST transpososome structures significantly enhances our understanding of CAST transposition systems and suggests avenues for improving CAST transposition for precision genome-editing applications.

biophysics↗