skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Granulocytes accumulate in resorbing tails of metamorphosing Xenopus laevis amphibians
Amphibian metamorphosis represents a dramatic example of post-embryonic development. In the anuran Xenopus laevis frog, this process involves extensive changes to larval tissues, structures, and physiology to produce its adult form. As a long-standing model to study tissue remodeling, both amphibian metamorphosis and mammalian development are under the control of thyroid hormone. Successful remodeling though, also requires precise temporospatial regulation of immune activation. Yet there is much to learn about the immune components linked to metamorphosis. In turn, granulocytes are a class of innate immune cells recently touted for their participation in processes beyond classical immune defenses, including in pathological and non-pathological tissue remodeling. In this manuscript, we explore the roles of granulocytes in perhaps the most conspicuous anuran metamorphic event: tadpole tail reabsorption. We characterize granulocyte infiltration into the tail as metamorphosis progresses. Although some granulocyte subpopulations exist in both Xenopus and mammals, our previous work has identified additional Xenopus-specific populations. Thus, here we further explored subpopulation dynamics through distinct stages of natural metamorphosis, their likely roles during this process, and their relationship with thyroid hormone. As endocrine disruptors continue to threaten species across the animal kingdom, the work described here offers much-needed insight into immune contributions to endocrine-linked development.  more » « less
Award ID(s):
1749427
PAR ID:
10522690
Author(s) / Creator(s):
; ; ; ; ;
Publisher / Repository:
Elseviere
Date Published:
Journal Name:
Comparative Immunology Reports
Volume:
6
Issue:
C
ISSN:
2950-3116
Page Range / eLocation ID:
200139
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Corticosteroids are critical for development and for mediating stress responses across diverse vertebrate taxa. Study of frog metamorphosis has made significant breakthroughs in our understanding of corticosteroid signaling during development in non-mammalian vertebrate species. However, lack of adequate corticosterone (CORT) response genes in tadpoles make identification and quantification of CORT responses challenging. Here, we characterized a CORT-response genefrzb(frizzled related protein) previously identified inXenopus tropicalistadpole tail skin by an RNA-seq study. We validated the RNA-seq results that CORT and not thyroid hormone inducesfrzbin the tails using quantitative PCR. Further, maximumfrzbexpression was achieved by 100-250 nM CORT within 12-24 hours.frzbis not significantly induced in the liver and brain in response to 100 nM CORT. We also found no change infrzbexpression across natural metamorphosis when endogenous CORT levels peak. Surprisingly,frzbis only induced by CORT inX. tropicalistails and not inXenopus laevistails. The exact downstream function of increasedfrzbexpression in tails in response to CORT is not known, but the specificity of hormone response and its high mRNA expression levels in the tail renderfrzba useful marker of exogenous CORT-response independent of thyroid hormone for exogenous hormone treatments andin-vivoendocrine disruption studies. 
    more » « less
  2. Protrusile jaws are a highly useful innovation that has been linked to extensive diversification in fish feeding ecology. Jaw protrusion can enhance the performance of multiple functions, such as suction production and capturing elusive prey. Identifying the developmental factors that alter protrusion ability will improve our understanding of fish diversification. In the zebrafish protrusion arises postmetamorphosis. Fish metamorphosis typically includes significant changes in trophic morphology, accompanies a shift in feeding niche and coincides with increased thyroid hormone production. We tested whether thyroid hormone affects the development of zebrafish feeding mechanics. We found that it affected all developmental stages examined, but that effects were most pronounced after metamorphosis. Thyroid hormone levels affected the development of jaw morphology, feeding mechanics, shape variation, and cranial ossification. Adult zebrafish utilize protrusile jaws, but an absence of thyroid hormone impaired development of the premaxillary bone, which is critical to jaw protrusion. Premaxillae from early juvenile zebrafish and hypothyroid adult zebrafish resemble those from adults in the generaDanionella, Devario, andMicrodevariothat show little to no jaw protrusion. Our findings suggest that evolutionary changes in how the developing skulls of danionin minnows respond to thyroid hormone may have promoted diversification into different feeding niches. 
    more » « less
  3. Global amphibian declines are largely driven by deadly disease outbreaks caused by the chytrid fungus, Batrachochytrium dendrobatidis (Bd). In the time since these disease outbreaks were first discovered, much has been learned about the roles of amphibian skin-produced antimicrobial components and skin microbiomes in controlling Bd. Yet almost nothing is known about the roles of skin-resident immune cells in anti-Bd defenses. Notably, mammalian mast cells reside within and serve as key immune sentinels in barrier tissues like the skin. Thus, they are critical to immune recognition of pathogens and to orchestrating the ensuing immune responses. Accordingly, we investigated the roles of Xenopus laevis frog mast cells during Bd infections. Our findings indicate that enrichment of X. laevis skin mast cells confers significant anti-Bd protection and ameliorates the inflammation-associated skin damage caused by Bd infection. Moreover, enriching X. laevis mast cells promotes greater mucin content within cutaneous mucus glands and protects frogs from Bd-mediated changes to their skin microbiomes. Together, this work underlines the importance of amphibian skin-resident immune cells in anti-Bd defenses and introduces a novel approach for investigating amphibian host-chytrid pathogen interactions. 
    more » « less
  4. The immune equilibrium model suggests that exposure to microbes during early life primes immune responses for pathogen exposure later in life. While recent studies using a range of gnotobiotic (germ-free) model organisms offer support for this theory, we currently lack a tractable model system for investigating the influence of the microbiome on immune system development. Here, we used an amphibian species ( Xenopus laevis ) to investigate the importance of the microbiome in larval development and susceptibility to infectious disease later in life. We found that experimental reductions of the microbiome during embryonic and larval stages effectively reduced microbial richness, diversity and altered community composition in tadpoles prior to metamorphosis. In addition, our antimicrobial treatments resulted in few negative effects on larval development, body condition, or survival to metamorphosis. However, contrary to our predictions, our antimicrobial treatments did not alter susceptibility to the lethal fungal pathogen Batrachochytrium dendrobatidis ( Bd ) in the adult life stage. While our treatments to reduce the microbiome during early development did not play a critical role in determining susceptibility to disease caused by Bd in X. laevis , they nevertheless indicate that developing a gnotobiotic amphibian model system may be highly useful for future immunological investigations. This article is part of the theme issue ‘Amphibian immunity: stress, disease and ecoimmunology’. 
    more » « less
  5. Abstract Amphibians undergo a variety of post‐embryonic transitions (PETr) that are partly governed by thyroid hormone (TH). Transformation into a terrestrial form follows an aquatic larval stage (biphasic) or precedes hatching (direct development). Some salamanders maintain larval characteristics and an aquatic lifestyle into adulthood (paedomorphosis), which obscures the conclusion of their larval period. Paedomorphic axolotls exhibit elevated TH during early development that is concomitant with transcriptional reprogramming and limb emergence. A recent perspective suggested this cryptic TH‐based PETr is uncoupled from metamorphosis in paedomorphs and concludes the larval period. This led to their question:“Are paedomorphs actual larvae?”. To clarify, paedomorphs are only considered larval in form, even though they possess some actual larval characteristics. However, we strongly agree that events during larval development inform amphibian life cycle evolution. We build upon their perspective by considering the evolution of limb emergence and metamorphosis. Limbless hatchling larval salamanders are generally associated with ponds, while limbed larvae are common to streams and preceded the evolution of direct development. Permian amphibians had limbed larvae, so their PETr was likely uncoupled from metamorphosis, equivalent to most extant biphasic and paedomorphic salamanders. Coupling of these events was likely derived in frogs and direct developing salamanders. 
    more » « less