Rediscovering the Axolotl as a Model for Thyroid Hormone Dependent Development - PubMed (original) (raw)

Rediscovering the Axolotl as a Model for Thyroid Hormone Dependent Development

Anne Crowner et al. Front Endocrinol (Lausanne). 2019.

Abstract

The Mexican axolotl (Ambystoma mexicanum) is an important model organism in biomedical research. Much current attention is focused on the axolotl's amazing ability to regenerate tissues and whole organs after injury. However, not forgotten is the axolotl's equally amazing ability to thwart aspects of tissue maturation and retain juvenile morphology into the adult phase of life. Unlike close tiger salamander relatives that undergo a thyroid hormone regulated metamorphosis, the axolotl does not typically undergo a metamorphosis. Instead, the axolotl exhibits a paedomorphic mode of development that enables a completely aquatic life cycle. The evolution of paedomorphosis allowed axolotls to exploit relatively permanent habitats in Mexico, and preadapted axolotls for domestication and laboratory study. In this perspective, we first introduce the axolotl and the various meanings of paedomorphosis, and then stress the need to move beyond endocrinology-guided approaches to understand the axolotl's hypothyroid state. With the recent completion of the axolotl genome assembly and established methods to manipulate gene functions, the axolotl is poised to provide new insights about paedomorphosis and the role of thyroid hormone in development and evolution.

Keywords: ambystoma; axolotl; metamorphosis; paedomorphosis; thyroid hormone.

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Figures

Figure 1

Figure 1

(A) The ancestral salamander mode of development is metamorphosis. Metamorphosis in the tiger salamander is regulated by the hypothalamus-pituitary-thyroid (HPT) axis. At a critical time during larval development, corticotrophin releasing hormone (CRH) from the hypothalamus stimulates thyrotrophic cells in the pituitary to release thyroid stimulating hormone (TSH), which in turn stimulates the thyroid gland to secrete thyroid hormone (TH). Increasing TH (+) triggers metamorphic changes in target cells. (B) The derived paedomorphic mode of development. Paedomorphosis in the axolotl results in the retention of ancestral larval characters into the adult phase of life. Although CRH-like and TSH-like activity are present in the axolotl hypothalamus and pituitary respectively, and TSH and TH treatment can induce metamorphosis, the HPT axis is not activated during larval development. Modified from Johnson and Voss (7).

Figure 2

Figure 2

(A) Map of genes from axolotl chromosome 2 (Chr2p) that associate with met1. (B) General structure of CCN family proteins showing insulin-like growth factor binding protein-like (IGFBP), a von Willebrand factor type C repeat (VWC), thrombospondin-homology type 1 repeat (TSP1), and a C-terminal cysteine-knot-containing (CT) domains. Human (Hs) ccn1 (GenBank: AAB84227.1) was used as a reference to compare domain-specific amino acid similarity among Xenopus tropicalis (Xp) ccn1 (GenBank: OCA36969.1), A. mexicanum ccn1 (AMEXTC_0340000257024_cysteine-rich), and A. mexicanum ccn1-like (AMEXTC_0340000025590_LOC102363594). The A. mexicanum ccn1-like sequence has a unique deletion of 30 amino acids between the VWC and TSP1 domains.

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