During terminal differentiation, most cells exit the cell cycle and enter into a prolonged or permanent G0 in which they are refractory to mitogenic signals. Entry into G0 is usually initiated ...through the repression of cell cycle gene expression by formation of a transcriptional repressor complex called dimerization partner (DP), retinoblastoma (RB)-like, E2F and MuvB (DREAM). However, when DREAM repressive function is compromised during terminal differentiation, additional unknown mechanisms act to stably repress cycling and ensure robust cell cycle exit. Here, we provide evidence that developmentally programmed, temporal changes in chromatin accessibility at a small subset of critical cell cycle genes act to enforce cell cycle exit during terminal differentiation in the Drosophila melanogaster wing. We show that during terminal differentiation, chromatin closes at a set of pupal wing enhancers for the key rate-limiting cell cycle regulators Cyclin E (cycE), E2F transcription factor 1 (e2f1), and string (stg). This closing coincides with wing cells entering a robust postmitotic state that is strongly refractory to cell cycle reactivation, and the regions that close contain known binding sites for effectors of mitogenic signaling pathways such as Yorkie and Notch. When cell cycle exit is genetically disrupted, chromatin accessibility at cell cycle genes remains unaffected, and the closing of distal enhancers at cycE, e2f1, and stg proceeds independent of the cell cycling status. Instead, disruption of cell cycle exit leads to changes in accessibility and expression of a subset of hormone-induced transcription factors involved in the progression of terminal differentiation. Our results uncover a mechanism that acts as a cell cycle-independent timer to limit the response to mitogenic signaling and aberrant cycling in terminally differentiating tissues. In addition, we provide a new molecular description of the cross talk between cell cycle exit and terminal differentiation during metamorphosis.
AbstractUnderstanding the evolution of development (evo-devo) in the Ophiuroidea and the pathways in the switch from a feeding to a nonfeeding larva is complicated by the variability in the phenotype ...of the metamorphic larva, being a reduced yolky ophiopluteus in some species (type I development) and a vitellaria larva in others (type II development). We investigated evo-devo in the family Ophionereididae, a group dominated by lecithotrophic development through a vitellaria larva. We reared the planktotrophic larvae of
to settlement to determine the metamorphic phenotype. Counter to expectations,
did not exhibit type II metamorphosis through a vitellaria, although it did exhibit transient vitellaria-like features. Resorption of the larval arms in the same interradial positions where the ciliary bands form in vitellariae gave them a fleeting vitellaria-like appearance. Development of
exhibits heterochronic features in early formation of the skeletal primordium of the third pair (postoral) of larval arms and in the presettlement juvenile early appearance of the juvenile terminal arm plates on external view in parallel with larval arm resorption. Development of the fourth pair (posterodorsal) of larval arms, the last pair to be formed, is plastic, with 44% of larvae exhibiting partial arm growth. Heterochronic traits in development, as seen in
, may have facilitated evolution of a lecithotrophic mode of development in
. Comparison of the ophiopluteus of
and the vestigial pluteus of
provided insights into the simplification of larval form from the ancestral (feeding larva) state in
. The diverse metamorphic phenotypes in ophiuroids indicate that type I and type II development may not be completely divergent lines of evo-devo and point to selective pressure in the pelagic-benthic transition in the evolution of ophiuroid development.
Changes in the amount, intensity, and timing of precipitation are increasing hydrologic variability in many regions, but we have little understanding of how these changes are affecting freshwater ...species. Stream-breeding amphibians—a diverse group in North America—may be particularly sensitive to hydrologic variability during aquatic larval and metamorphic stages. Here, we tested the prediction that hydrologic variability in streams decreases survival through metamorphosis in the salamander Gyrinophilus porphyriticus, reducing recruitment to the adult stage. Using a 20-y dataset from Merrill Brook, a stream in northern New Hampshire, we show that abundance of G. porphyriticus adults has declined by ∼50% since 1999, but there has been no trend in larval abundance. We then tested whether hydrologic variability during summers influences survival through metamorphosis, using capture–mark–recapture data from Merrill Brook (1999 to 2004) and from 4 streams in the Hubbard Brook Experimental Forest (2012 to 2014), also in New Hampshire. At both sites, survival through metamorphosis declined with increasing variability of stream discharge. These results suggest that hydrologic variability reduces the demographic resilience and adaptive capacity of G. porphyriticus populations by decreasing recruitment of breeding adults. They also provide insight on how increasing hydrologic variability is affecting freshwater species, and on the broader effects of environmental variability on species with vulnerable metamorphic stages.
Whenever genetically correlated traits experience antagonistic selection, an adaptive response in one trait can lead to a maladaptive response in the correlated trait. This is a form of genome-level ...conflict that can have important evolutionary consequences by impeding organisms from reaching their adaptive optima. Antagonistic selection should be pervasive in organisms with complex life histories because larval and adult life stages specialize in dramatically different environments. Since individuals express larval and adult morphologies from a single genome, genomic conflict across ontogenetic stages should also be prevalent. Using wood frogs as a study system, we measured natural selection on larval and postmetamorphic life stages and estimated genetic correlations among traits. Alternative life stages experienced a mix of both antagonistic and congruent viability selection. The integration between traits changed over the course of metamorphosis, reducing genetic correlations that cause conflict. Our results provide novel experimental evidence that metamorphosis can alleviate genomic conflict by partitioning life-history stages into modules that can more readily respond to selection. These results highlight the adaptive potential of metamorphosis as a means to avoid ecological specialization trade-offs. Moreover, they provide insights into the prevalence and evolutionary maintenance of complex life cycles.
Like many other cnidarians, corals undergo metamorphosis from a motile planula larva to a sedentary polyp. In some sea anemones such as Nematostella this process is a smooth transition requiring no ...extrinsic stimuli, but in many corals it is more complex and is cue-driven. To better understand the molecular events underlying coral metamorphosis, competent larvae were treated with either a natural inducer of settlement (crustose coralline algae chips/extract) or LWamide, which bypasses the settlement phase and drives larvae directly into metamorphosis. Microarrays featuring >8000 Acropora unigenes were used to follow gene expression changes during the 12h period after these treatments, and the expression patterns of specific genes, selected on the basis of the array experiments, were investigated by in situ hybridization. Three patterns of expression were common—an aboral pattern restricted to the searching/settlement phase, a second phase of aboral expression corresponding to the beginning of the development of the calicoblastic ectoderm and continuing after metamorphosis, and a later orally-restricted pattern.
► We examined the response of coral larvae to inducers of settlement and metamorphosis. ► Initially metamorphosis proceeds in the absence of substantial transcriptional change. ► Differentially expressed genes show three spatial patterns at settlement. ► Coral metamorphosis involves many of “the usual suspects” plus novel genes.
Regeneration of lost cells in the central nervous system, especially the brain, is present to varying degrees in different species. In mammals, neuronal cell death often leads to glial cell ...hypertrophy, restricted proliferation, and formation of a gliotic scar, which prevents neuronal regeneration. Conversely, amphibians such as frogs and salamanders and teleost fish possess the astonishing capacity to regenerate lost cells in several regions of their brains. While frogs lose their regenerative abilities after metamorphosis, teleost fish and salamanders are known to possess regenerative competence even throughout adulthood. In the last decades, substantial progress has been made in our understanding of the cellular and molecular mechanisms of brain regeneration in amphibians and fish. But how similar are the means of brain regeneration in these different species? In this review, we provide an overview of common and distinct aspects of brain regeneration in frog, salamander, and teleost fish species: from the origin of regenerated cells to the functional recovery of behaviors.
Juvenile hormones (JHs) are sesquiterpenoids synthesized by the corpora allata (CA). They play critical roles during insect development and reproduction. The first JH was described in 1934 as a ..."metamorphosis inhibitory hormone" in Rhodnius prolixus by Sir Vincent B. Wigglesworth. Remarkably, in spite of the importance of R. prolixus as vectors of Chagas disease and model organisms in insect physiology, the original JH that Wigglesworth described for the kissing-bug R. prolixus remained unidentified. We employed liquid chromatography mass spectrometry to search for the JH homologs present in the hemolymph of fourth instar nymphs of R. prolixus. Wigglesworth's original JH is the JH III skipped bisepoxide (JHSB3), a homolog identified in other heteropteran species. Changes in the titer of JHSB3 were studied during the 10-day long molting cycle of 4
instar nymph, between a blood meal and the ecdysis to 5
instar. In addition we measured the changes of mRNA levels in the CA for the 13 enzymes of the JH biosynthetic pathway during the molting cycle of 4
instar. Almost 90 years after the first descriptions of the role of JH in insects, this study finally reveals that the specific JH homolog responsible for Wigglesworth's original observations is JHSB3.
The steroid hormone ecdysone is the central regulator of insect metamorphosis, during which a growing, immature larva is remodeled, through pupal stages, to a reproductive adult. However, the ...underlying mechanisms of ecdysone‐mediated metamorphosis remain to be fully elucidated. Here, we identified metamorphosis‐associated microRNAs (miRNAs) and their potential targets by cross‐linking immunoprecipitation coupled with deep sequencing of endogenous Argonaute 1 protein in Drosophila. Interestingly, miR‐8‐3p targeted five Vha genes encoding distinct subunits of vacuolar H+‐ATPase (V‐ATPase), which has a vital role in the organellar acidification. The expression of ecdysone‐responsive miR‐8‐3p is normally downregulated during Drosophila metamorphosis, but temporary overexpression of miR‐8‐3p in the whole body at the end of larval development led to defects in metamorphosis and survival, hallmarks of aberrant ecdysone signaling. In addition, miR‐8‐3p was expressed in the prothoracic gland (PG), which produces and releases ecdysone in response to prothoracicotropic hormone (PTTH). Notably, overexpression of miR‐8‐3p or knockdown of its Vha targets in the PG resulted in larger than normal, ecdysone‐deficient larvae that failed to develop into the pupal stage but could be rescued by ecdysone feeding. Moreover, these animals showed defective PTTH signaling with a concomitant decrease in the expression of ecdysone biosynthetic genes. We also demonstrated that the regulatory network between the conserved miR‐8‐3p/miR‐200 family and V‐ATPase was functional in human cells. Consequently, our data indicate that the coordinated regulation of V‐ATPase subunits by miR‐8‐3p is involved in Drosophila metamorphosis by controlling the ecdysone biosynthesis.
Genome size varies widely among organisms and is known to affect vertebrate development, morphology, and physiology. In amphibians, genome size is hypothesized to contribute to loss of late-forming ...structures, although this hypothesis has mainly been discussed in salamanders. Here we estimated genome size for 22 anuran species and combined this novel data set with existing genome size data for an additional 234 anuran species to determine whether larger genome size is associated with loss of a late-forming anuran sensory structure, the tympanic middle ear. We established that genome size is negatively correlated with development rate across 90 anuran species and found that genome size evolution is correlated with evolutionary loss of the middle ear bone (columella) among 241 species (224 eared and 17 earless). We further tested whether the development of the tympanic middle ear could be constrained by large cell sizes and small body sizes during key stages of tympanic middle ear development (metamorphosis). Together, our evidence suggests that larger genomes, slower development rate, and smaller body sizes at metamorphosis may contribute to the loss of the anuran tympanic middle ear. We conclude that increases in anuran genome size, although less drastic than those in salamanders, may affect development of late-forming traits.
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