The role of thyroid hormone in zebrafish and axolotl development - PubMed (original) (raw)

The role of thyroid hormone in zebrafish and axolotl development

D D Brown. Proc Natl Acad Sci U S A. 1997.

Abstract

Exogenous thyroid hormone (TH) induces premature differentiation of the zebrafish pectoral fins, which are analogous to the forelimbs of tetrapods. It accelerates the growth of the pelvic fins but not precociously. Goitrogens, which are chemical inhibitors of TH synthesis by the thyroid gland, inhibit the transition from larva to juvenile fish including the formation of scales, and pigment pattern; they stunt the growth of both pectoral and pelvic paired fins. Inhibition by goitrogens is rescued by the simultaneous addition of thyroxine. The effect of adding TH to the rearing water of the postembryonic Mexican axolotl was reinvestigated under conditions that permit continued growth and development. In addition to morphological changes that have been described, TH greatly stimulates axolotl limb growth causing the resulting larva to be proportioned as an adult in about two months. This study extends the known evolutionary relatedness of tetrapod limbs and fish fins to include the TH stimulation of salamander limb and zebrafish fin growth, and suggests that TH is required to complete the life cycle of a typical bony fish and a salamander at the same developmental stage that it controls anuran and flounder metamorphosis.

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Figures

Figure 1

Figure 1

(Upper) Two-week-old (4 mm) larva. (Lower) Three-week-old juvenile (6 mm) beginning unpaired fin development. Stained with alcian blue and alizarin red. Ossification has not begun. The larval paired pectoral fins are not visible in this side view.

Figure 2

Figure 2

Premature development of the paired pectoral fins induced by exogenous T4. Larvae were treated continuously with 30 nM T4 beginning 11 days postfertilization. Upper, the two animals (length, 6.5 mm) were fixed 23 days postfertilization. Lower, the two animals (8.5 mm) were fixed several days later.

Figure 3

Figure 3

The effect of thyroxine on the early larval development of the axolotl. The same control and 30 nM T4-treated (TH) sibling animals were photographed at the days postfertilization noted. T4 was added from day 14. (Bar = 1 cm.)

Figure 5

Figure 5

The effect of goitrogens on zebrafish metamorphosis and rescue by T4. (A) Dorsal and (B) side views of sibling fish fixed and stained with alcian/alizarin on day 33 postfertilization: (Top) control; (Middle) treated continuously from day 4 with 1 mM methimazole; (Bottom) treated similarly with methimazole but rescued by the addition of 30 nM T4 beginning at day 11. (C) Sibling fish were fixed and stained with alician/alizarin at day 65 postfertilization: (Top) control; (Middle) treated continuously from day 14 with 0.025% KClO4; (Bottom) treated similarly with KClO4 but rescued by the addition of 30 nM T4 beginning at day 56. (Bar = 3 mm.)

Figure 4

Figure 4

Thyroid gland function assessed by [125]I uptake. (A) Developmental series in days postfertilization. (B) Goitrogens and/or 20nM T4 added on day 4 and radioiodide uptake on day 24. Lanes: 1, control; 2, 1 mM methimazole; 3, 1 mM methimazole and 20 nM T4; 4, 20 nM T4; and 5, 1 mM methimazole until day 12 then control until day 24. (C) Four different goitrogens were added at day 12 postfertilization; radioiodide uptake was assayed on day 33. Inhibitor concentrations were: 0.005% 6-n-propyl-2-thiouracil, 0.003% TU, 0.05% KClO4, and 0.3 mM methimazole.

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