Biology subjects

Qi, Y. B.

Publications and source records attributed to Qi, Y. B..

4 recordsLinked to original sources

bioRxiv2026

MYRF drives heterochronic miRNAs and LIN-42, and amplifies oscillatory programs for stage transitions

Larval development in C. elegans proceeds through discrete stages, yet the mechanisms that drive stage transitions remain incompletely defined. Here, we identify the transmembrane transcription factor MYRF as a master temporal regulator essential for larval progression. MYRF cleavage and nuclear accumulation oscillate across larval stages, peaking during mid-to-late intermolt phases. MYRF directly activates key heterochronic microRNAs--including lin-4, mir-48/241/84, and let-7--and amplifies the oscillatory gene network by promoting central regulators such as nhr-23. MYRF loss-of-function or acute depletion suppresses and flattens this network, causing developmental arrest during the late intermolt phase of each larval cycle and stalling molting, seam cell division, and vulval morphogenesis. Notably, MYRF oscillations precede and induce activation of lin-42/Period, which feeds back to repress myrf, sharpening oscillatory precision. Together, these findings establish MYRF as a central driver of larval stage transitions, coupling microRNA-conferred temporal identity with an amplifier-based logic that executes stage- and phase-specific developmental programs.

developmental biology↗

bioRxiv2026

Dual Inhibition of MYRF Cleavage by Its JM Region and PAN-1 CCT Gates Developmental Timing in C. elegans

Post-embryonic development proceeds through discrete stages, yet the mechanisms that coordinate transitions between stages remain incompletely defined. The transmembrane transcription factor MYRF undergoes intramolecular cleavage to release a nuclear-localized fragment essential for developmental progression in C. elegans. Previously, we showed that PAN-1 as a key partner required for MYRF activity during development. PAN-1 promotes MYRF trafficking to the cell membrane--an essential step for MYRF cleavage--through interactions between their extracellular domains (Xia et al., 2021). Here, we show that MYRF-1 cleavage and nuclear translocation oscillate with larval stage transitions in C. elegans, peaking mid-to-late stage and being suppressed during molts. Using endogenous gene editing and mutant reporters, we identify an uncharacterized juxtamembrane (JM) region in MYRF-1 that self-inhibits cleavage. JM deletion triggers premature MYRF-1 nuclear entry, early lin-4 activation, growth defects, and adult lethality. We further demonstrate that the cytoplasmic tail (CCT) of the transmembrane protein PAN-1 acts as a predominant trans-inhibitor of MYRF-1 cleavage, coupling extracellular association with cytoplasmic inhibition. PAN-1 CCT deletion causes near-constitutive MYRF-1 nuclear accumulation, leading to premature lin-4 activation, accelerated M-cell division, and larval lethality. Removing these inhibitory mechanisms on MYRF-1 cleavage overrides nutrient-responsive developmental checkpoints. These findings uncover dual inhibitory mechanisms governing MYRF-1 cleavage and establish MYRF-1 cleavage as a key gatekeeper of developmental timing.

developmental biology↗

bioRxiv2024

Somatic Transthyretin-Related Proteins in C. elegans Govern Reproductive Longevity by Sustaining Sperm Integrity and Timely Ovulation

The decline in reproductive capability during adult life is critical for health, but its mechanism is elusive. We systematically analyzed the developmental role of an expanded TTR family of proteins, structurally analogous to mammalian thyroid hormone-transporting Transthyretin, and identified three paralogous proteins, TTR-15, TTR-16, and TTR-17, differentially expressed in somatic cells of the gonads and secreted around gametes in C. elegans. Simultaneous inactivation of TTR-15, TTR-16, and TTR-17 leads to a rapid reduction in reproductive capacity in middle age. While oocyte and sperm production remain unaffected in the triple mutants, late-onset infertility results from stalled ovulation. Mechanistically, the absence of TTR-15, TTR-16, and TTR-17 causes sperm to prematurely deplete the cytoplasmic pool of major sperm protein (MSP), released via non-conventional vesicle budding as a signal for ovulation. We propose that the somatic gonads play a central role in maintaining sperm integrity post-production and determining the duration of the reproductive age. HighlightsO_LISystematic analysis of TTR family proteins reveals diverse expression and critical functions. C_LIO_LITTR-15, TTR-16, and TTR-17 are secreted around gametes in C. elegans. C_LIO_LITTR-15/16/17 triple KO exhibits middle-age onset infertility due to stalled ovulation. C_LIO_LIMSP, a signal for ovulation, is prematurely depleted from sperm in the absence of TTR-15/16/17. C_LI

developmental biology↗

bioRxiv2017

Excitatory Motor Neurons Function As Central Pattern Generators In An Anatomically Compressed Motor Circuit For Reverse Locomotion

Central pattern generators are cell- or network-driven oscillators that underlie motor rhythmicity. The existence and identity of C. elegans CPGs are unknown. Through cell ablation, electrophysiology, and calcium imaging, we identified oscillators for C. elegans reverse locomotion. We show that the cholinergic and excitatory class A motor neurons exhibit intrinsic and oscillatory activity, and such an activity can drive reverse locomotion without premotor interneurons. Regulation of their oscillatory activity, either through effecting the P/Q/N high voltage-activated calcium channel, an endogenous constituent of their intrinsic oscillation, or, via the dual regulation by descending premotor interneurons, determines the propensity, velocity, and sustention of reverse locomotion. Thus, the reversal motor neuron themselves serve as distributed local oscillators; regulation of their intrinsic activity controls the reversal motor state. These findings exemplify anatomic and functional compression: motor executors integrate the role of rhythm generation in a locomotor network that is constrained by small cell numbers.\n\nHighlightsO_LIThe class A motor neurons (A-MNs) intrinsically oscillate.\nC_LIO_LIHigh voltage-activated calcium channel is a constituent of A-MN oscillation.\nC_LIO_LIRegulation of A-MN oscillation by interneurons determines the reversal state.\nC_LIO_LIA-MNs integrate the role of multiple neuron types in large locomotor networks.\nC_LI

neuroscience↗