Biology subjects

Yette, G. A.

Publications and source records attributed to Yette, G. A..

4 recordsLinked to original sources

bioRxiv2025

Sonic hedgehog signaling promotes basal epidermal fibrillin 3 expression for zebrafish fin ray branching

Zebrafish robustly regenerate amputated fins, including restoring branched bony ray skeletons. During fin outgrowth, sonic hedgehog a (shha)-expressing basal epidermal cells (bEps) signal to themselves and adjacent progenitor osteoblasts (pObs) to progressively split pObs into daughter ray pools. Collectively moving bEps pass through a shha-expressing state to define distal shha- positive bEp domains that themselves separate laterally ahead of ray branching. As such, Shh/Smo signaling may promote transient associations between bEps and pObs that gradually splits pOb pools. We used bulk RNA sequencing of caudal fin regenerates after Smoothened (Smo) inhibition followed by a CRISPant screen to identify fibrillin 3 (fbn3) as a candidate Shh/Smo target gene for ray branching. Homozygous fbn3 mutant zebrafish regenerated caudal fins with fewer branched rays and increased distances to branch points. Shh/Smo signaling was required specifically for full fbn3 induction in bEps but not pObs. Double mutants showed that fibrillin 2 (fbn2; FBN2 ortholog) redundantly supports fbn3-promoted ray branching. Fbn1-containing microfibrils accumulated at the bEp/pOb interface in fbn3 and, more so, fbn3/2 mutant regenerating caudal fins. Shh/Smo signaling may activate bEp fbn3 expression to locally modify microfibril abundance, facilitating bEp-pOb interactions and/or movements underlying ray branching morphogenesis.

developmental biology↗

bioRxiv2021

Zebrafish Polycomb repressive complex-2 critical roles are largely Ezh2- over Ezh1-driven and concentrate during early embryogenesis

Polycomb repressive complex-2 (PRC2) methylation of histone H3 lysine-27 (H3K27me) is associated with stable transcriptional repression. PRC2 famously silences Hox genes to maintain anterior-posterior segment identities but also enables early cell fate specification, restrains progenitor cell differentiation, and canalizes cell identities. Zebrafish PRC2 genetic studies have focused on ezh2, which, with its paralog ezh1, encodes the H3K27 methyltransferase component. ezh2 loss-of-function mutants reinforce essential vertebrate PRC2 functions during early embryogenesis albeit with limited contributions to body plan establishment. However, redundancy with ezh1 and the lethality of maternal-zygotic homozygous ezh2 nulls could obscure additional early developmental and organogenesis roles of PRC2. Here, we combine new and existing zebrafish ezh1 and ezh2 alleles to show collective maternal/zygotic ezh2 exclusively provides earliest embryonic PRC2 H3K27me3 activity. Zygotic ezh1, which becomes progressively expressed as ezh2 levels dissipate, has minor redundant and noncompensatory larval roles but itself is not required for viability or fertility. Zygotic Ezh2/PRC2 promotes correct craniofacial bone shape and size by maintaining proliferative pre-osteoblast pools. An ezh2 allelic series including disrupted maternal ezh2 uncovers axial skeleton homeotic transformations and pleiotropic organogenesis defects. Further, once past a critical early window, we show zebrafish can develop near normally with minimal bulk H3K27me3. Our results suggest Ezh2-containing PRC2 stabilizes rather than instructs early developmental decisions while broadly contributing to organ size and embellishment.

developmental biology↗

bioRxiv2019

longfin causes cis-ectopic expression of the kcnh2a ether-a-go-go K+ channel to autonomously prolong fin outgrowth

Organs stop growing to achieve a characteristic size and shape in scale with the animals body. Likewise, regenerating organs sense injury extents to instruct appropriate replacement growth. Fish fins exemplify both phenomena through their tremendous diversity of form and remarkably robust regeneration. The classic zebrafish mutant longfint2 develops and regenerates dramatically elongated fins and underlying ray skeleton. We show longfint2 chromosome 2 overexpresses the ether-a-go-go-related voltage-gated potassium channel kcnh2a. Genetic disruption of kcnh2a in cis rescues longfint2, indicating longfint2 is a regulatory kcnh2a allele. We find longfint2 fin overgrowth originates from prolonged outgrowth periods including by showing Kcnh2a chemical inhibition during late stage regeneration fully suppresses overgrowth. Cell transplantations demonstrate longfint2-ectopic kcnh2a acts tissue autonomously within the fin intra-ray mesenchymal lineage. Temporal inhibition of the Ca2+-dependent phosphatase calcineurin indicates it likewise entirely acts late in regeneration to attenuate fin outgrowth. Epistasis experiments suggest longfint2-expressed Kcnh2a inhibits calcineurin output to supersede growth cessation signals. We conclude ion signaling within the growth-determining mesenchyme lineage controls fin size by tuning outgrowth periods rather than altering positional information or cell-level growth potency.

developmental biology↗

bioRxiv2019

Transpositional scaling and niche transitions restore organ size and shape during zebrafish fin regeneration

Regenerating fish fins return to their original size and shape regardless of the nature or extent of injury. Prevailing models for this longstanding mystery of appendage regeneration speculate fin cells maintain uncharacterized positional identities that instruct outgrowth after injury. Using zebrafish, we find differential Wnt production correlates with the extent of regeneration across the caudal fin. We identify Dachshund transcription factors as markers of distal blastema cells that produce Wnt and thereby promote a pro-progenitor and -proliferation environment. We show these Dach-expressing \"niche cells\" derive from mesenchyme populating cylindrical and progressively tapered fin rays. The niche pool, and consequently Wnt, steadily dissipates as regeneration proceeds; once exhausted, ray and fin growth stops. Supported by mathematical modeling, we show longfint2 zebrafish regenerate exceptionally long fins due to a perdurant niche, representing a \"broken countdown timer\". We propose regenerated fin size is dictated by the amount of niche formed upon damage, which simply depends on the availability of intra-ray mesenchyme defined by skeletal girth at the injury site. Likewise, the fin reestablishes a tapered ray skeleton because progenitor osteoblast output reflects diminishing niche size. This \"transpositional scaling\" model contends mesenchyme-niche state transitions and positional information provided by self-restoring skeletal geometry rather than cell memories determine a regenerated fins size and shape.

developmental biology↗