Insulin-like growth factor signaling regulates developmental trajectory associated with diapause in embryos of the annual killifish Austrofundulus limnaeus

Abstract

Annual killifishes exhibit a number of unique life history characters including the occurrence of embryonic diapause, unique cell movements associated with dispersion and subsequent reaggregation of the embryonic blastomeres, and a short postembryonic life span. Insulin-like growth factor (IGF) signaling is known to play a role in the regulation of metabolic dormancy in a number of animals but has not been explored in annual killifishes. The abundance of IGF proteins during development and the developmental effects of blocking IGF signaling by pharmacological inhibition of the insulin-like growth factor I receptor (IGF1R) were explored in embryos of the annual killifish Austrofundulus limnaeus. Blocking of IGF signaling in embryos that would normally escape entrance into diapause resulted in a phenotype that was remarkably similar to that of embryos entering diapause. IGF-I protein abundance spikes during early development in embryos that will not enter diapause. In contrast, IGF-I levels remain low during early development in embryos that will enter diapause II. IGF-II protein is packaged at higher levels in escape-bound embryos compared with diapause-bound embryos. However, IGF-II levels quickly decrease and remain low during early development and only increase substantially during late development in both developmental trajectories. Developmental patterns of IGF-I and IGF-II protein abundance under conditions that would either induce or bypass entrance into diapause are consistent with a role for IGF signaling in the regulation of developmental trajectory and entrance into diapause in this species. We propose that IGF signaling may be a unifying regulatory pathway that explains the larger suite of characters that are associated with the complex life history of annual killifishes.

Temperature-dependent vitamin D signaling regulates developmental trajectory associated with diapause in an annual killifish

“…Transcriptome and WGCNA Analysis. RNA extraction, sequencing, and processing were performed as described previously (8). Gene counts were normalized as fragments per kilobase of transcript per million mapped reads (FPKM).…”

“…Exposure to increased temperature (30°C compared with 20°C to 25°C) and light promotes the escape trajectory (6,7). Biochemically, the trajectories diverge early in development, before the formation of the embryonic axis, as evidenced by reduced insulinlike growth factor (IGF) expression in diapause-bound embryos (8). A critical window of development where increased temperature causes irreversible commitment to the escape trajectory occurs during early somitogenesis in embryos possessing 10 to 20 pairs of somites.…”

The African turquoise killifish: A research organism to study vertebrate aging and diapause

“…This exaggerated phenotype is very rare in vertebrates that can do diapause, even among killifishes, and it makes the study of the impact of diapause on aging easier. Indeed, while other longer lived killifishes have been historically employed to study diapause, most of these studies have been focused on the stress resistant feature of diapause rather than its “aging resistance” (Meller, Meller, Simon, Culpepper & Podrabsky, 2012; Podrabsky & Hand, 1999, 2000; Woll & Podrabsky, 2017). Thus, the turquoise killifish provides a unique platform to address many critical questions of vertebrate diapause, including if there are shared components between diapause and normal aging (Reichwald et al., 2015), if and how the aging process is blocked during diapause, and if there is any tradeoff between the long‐term survival in diapause and the physiological status in adulthood.…”

Small noncoding RNA profiles along alternative developmental trajectories in an annual killifish

“…The development of A. limnaeus and other annual killifishes is unique among vertebrates because two alternative developmental trajectories that differ morphologically, physiologically, and biochemically are known to exist 21 – 23 . One trajectory leads to discontinuous development and the production of embryos that enter into a profound state of metabolic depression known as diapause, while the other trajectory supports continuous development to the pre-hatching stage in embryos that “escape” arrest in diapause (Fig.…”