Biology subjects

McMenamin, S. K.

Publications and source records attributed to McMenamin, S. K..

4 recordsLinked to original sources

bioRxiv2026

Notch-mediated thyroid hormone regulation of skin development in the zebrafish caudal fin

Thyroid hormone (TH) is a systemic regulator of vertebrate development, yet its role in the maturation of the stratified skin remains poorly defined. Using the skin at the edge of the zebrafish caudal fin, we defined the trajectory of epidermal maturation during the transition from juvenile to adult. We found the peripheral edge (PE) of the fin exhibits positive allometric expansion that is dependent on TH: in thyroid-ablated, hypothyroid backgrounds, the growth of the PE is limited. We showed that TH drives normal PE growth by stimulating both cell proliferation and hypertrophy. Further, we demonstrated that TH acts upstream of the Notch pathway to regulate growth of the PE. While TH signaling machinery is broadly expressed throughout the fin, Notch pathway activation is localized and highly enriched in the PE. Repressing Notch activity prevented PE expansion, while upregulating Notch in a hypothyroid background was sufficient to increase hypertrophy and partially rescue PE expansion. By identifying Notch as a region-specific effector of TH-driven hypertrophy, our findings show a mechanism by which systemic endocrine signals are translated into local tissue morphogenesis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/713269v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1381159org.highwire.dtl.DTLVardef@1fb2421org.highwire.dtl.DTLVardef@100fed3org.highwire.dtl.DTLVardef@5a0480_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2024

Adult caudal fin shape is imprinted in the embryonic fin fold

Appendage shape is formed during development (and re-formed during regeneration) according to spatial and temporal cues that orchestrate local cellular morphogenesis. The caudal fin is the primary appendage used for propulsion in most fish species, and exhibits a range of distinct morphologies adapted for different swimming strategies, however the molecular mechanisms responsible for generating these diverse shapes remain mostly unknown. In zebrafish, caudal fins display a forked shape, with longer supportive bony rays at the periphery and shortest rays at the center. Here, we show that a premature, transient pulse of sonic hedgehog a (shha) overexpression during late embryonic development results in excess proliferation and growth of the central rays, causing the adult caudal fin to grow into a triangular, truncate shape. Both global and regional ectopic shha overexpression are sufficient to alter fin shape, and forked shape may be rescued by subsequent treatment with an antagonist of the canonical Shh pathway. The induced truncate fins show a decreased fin ray number and fail to form the hypural diastema that normally separates the dorsal and ventral fin lobes. While forked fins regenerate their original forked morphology, truncate fins regenerate truncate, suggesting that positional memory of the fin rays can be permanently altered by a transient treatment during embryogenesis. Ray finned fish have evolved a wide spectrum of caudal fin morphologies, ranging from truncate to forked, and the current work offers insights into the developmental mechanisms that may underlie this shape diversity.

developmental biology↗

bioRxiv2019

Thyroid hormone coordinates developmental trajectories but does not underlie developmental truncation in Danionins

BackgroundChanges in post-embryonic developmental trajectories can profoundly alter adult phenotypes and life history transitions. In vertebrate clades with complex, biphasic life cycles, thyroid hormone (TH) regulates metamorphosis, and alterations to TH metabolism underlie famous cases of paedomorphosis. We tested the requirement for TH in multiple post-embryonic developmental processes in the zebrafish, and asked if TH loss was associated with paedomorphosis in miniaturized Danionellas. ResultsWe found that TH regulates the relative growth of different body parts in zebrafish, inhibiting head growth at juvenile stages. The lateral line also showed sensitivity to the hormone: head neuromasts were inhibited by TH, while trunk neuromasts required TH for their proliferation. While several aspects of Danionella morphology resembled that of larval zebrafish, these species did not resemble hypothyroid zebrafish in their shape or lateral line, and these fish showed functional thyroid follicles. ConclusionsAlthough zebrafish do not undergo a discrete ecological transformation, we found that multiple tissues go through a protracted metamorphosis, and that TH ushers in growth patterns and processes typical of juveniles. We found no evidence that compromised TH metabolism is responsible for paedomorphosis in Danionellas. Nonetheless, modulations to TH-sensitive pathways affect evolutionarily-relevant traits, and are likely important targets for adaptation. Bullet PointsO_LIThyroid hormone regulates shifts in relative growth trajectories in different zebrafish tissues C_LIO_LIThyroid hormone inhibits head growth in juvenile zebrafish, and regulates juvenile growth patterns C_LIO_LIThyroid hormone stimulates formation of neuromast canals in the head and stitches on the trunk of zebrafish C_LIO_LIDanionella, the miniaturized sister group to Danio morphologically resemble larval zebrafish and do not form neuromast canals C_LIO_LIHypothyroidism is not the cause of paedomorphosis in Danionella C_LI Grant SponsorsNIH R00GM105874 NIH R03HD091634 Burroughs Wellcome Collaborative Research Travel Grant 1017439

developmental biology↗

bioRxiv2017

microCT-Based Skeletal Phenomics in Zebrafish Reveals Virtues of Deep Phenotyping at the Whole-Organism Scale

Phenomics, which ideally involves in-depth phenotyping at the whole-organism scale, may enhance our functional understanding of genetic variation. Here, we demonstrate methods to profile hundreds of measures comprised of morphological and densitometric traits from a large number sites in the axial skeleton of adult zebrafish. We show the potential for vertebral patterns to confer heightened sensitivity, with similar specificity, in discriminating mutant populations compared to analyzing individual vertebrae in isolation. We identify phenotypes associated with human brittle bone disease and thyroid stimulating hormone receptor hyperactivity. Finally, we develop allometric models and show their potential to aid in the discrimination of mutant phenotypes masked by alterations in growth. Our studies demonstrate virtues of deep phenotyping in a spatially distributed organ. Analyzing phenotypic patterns may increase productivity in genetic screens, and could facilitate the study of genetic variants associated with smaller effect sizes, such as those that underlie complex diseases.

genetics↗