Deiodinase Activity Is Present inXenopus laevisduring Early Embryogenesis

Abstract

Thyroid hormones orchestrate amphibian metamorphosis. The type 2 and type 3 deiodinases make vital contributions to this process by controlling levels of the thyroid hormones T(4) and T(3) available to different tissues. Because the tadpole thyroid gland is not functional until stage NF44, it has been widely assumed that thyroid signaling is absent during amphibian early development, thyroid hormone only becoming a major regulator during premetamorphic stages. Similarly, in mammals, thyroid function is known to be essential to neuronal development, especially during the perinatal stages, but again little is known about early stages of development. Here we demonstrate that key elements of thyroid hormone signaling are present during early development of Xenopus. In particular, we find functional thyroid hormone-activating deiodinases and significant levels of their substrates, T(4) and T(3), during early embryogenesis. Furthermore, we have further characterized a recently identified deiodinase in amphibians, homologous to mammalian type 1 deiodinase (D1). This enzyme is expressed in marked, spatially defined patterns during embryogenesis. The patterns of expression of type 1 deiodinase are distinct from those of type 2 and type 3 deiodinases. Deiodinase expression is found in neurogenic areas from stage NF30 onward, both in the central and peripheral nervous systems. We conclude that both activating and inactivating deiodinases show dynamic patterns of expression during early embryogenesis in amphibians, particularly in neurogenic areas. These findings suggest that thyroid hormone signaling is a key component of early neuronal development in vertebrates.

Thyroid Hormone Receptor α Controls Developmental Timing and Regulates the Rate and Coordination of Tissue-Specific Metamorphosis in Xenopus tropicalis

“…First, TR α knockout accelerated premetamorphic development, enabling the animals to initiate metamorphosis earlier. Because T3 levels prior to stage 54 are very low compared with levels during metamorphosis (55, 69), TR α likely functions as unliganded TR to repress target gene expression. Indeed, of the T3-inducible genes that we have analyzed, all were found to be derepressed upon TR α knockout, and accompanied by reduced recruitment of the corepressor NCoR.…”

Perchlorate disrupts embryonic androgen synthesis and reproductive development in threespine stickleback without changing whole-body levels of thyroid hormone

“…The biological mechanisms of contaminant-induced phenotypic abnormalities are largely unknown, however. In particular, interactions of the HPT axis with other endocrine axes and developmental pathways are still poorly understood in many vertebrates, although it is clear that early developmental disruption of thyroid signaling would be deleterious in mammalian (Préau et al,, 2014) and non-mammalian vertebrates (Morvan Dubois et al, 2006; Préau et al, 2014). Consequently, the full suite of developmental and reproductive abnormalities caused by HPT disruption is still unknown for most contaminants.…”

Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

“…Mixture exposure (72 h) modified expression of multiple genes, including those encoding the deiodinases (enzymes that determine T 3 bioavailability)19, thyroid hormone receptors (TRs), thyroid hormone transporters (THTs) and genes implicated in neural stem cell renewal and neuronal differentiation. Expression of dio1, encoding deiodinase1 (D1, an activating or inactivating deiodinase)20, was significantly decreased, whilst expression of dio2, encoding deiodinase2 (D2, an activating enzyme) was increased (Fig. 3a,b) as suggested in Fig.…”

“…Mercury chelates selenium29, an element required for synthesis and activity of all deiodinases30. This feature links mercury to interference with thyroid hormone activation/inactivation via deiodination, through selenocysteine deiodinases that are active in Xenopus tadpoles at this developmental stage2031. These enzymes finely tune the bioavailability of the active form of thyroid hormone (T 3 ) in each cell.…”