Subterranean Fishes of the World

4296

2019

AIM 2019

48

Internal organs are positioned asymmetrically across the left-right (L-R) axis in all vertebrates. LR axis asymmetry arises early during development via the expression of conserved genes and signals relayed from an L-R organizer through the lateral plate mesoderm (LPM) and endoderm, resulting in the formation of L-R patterns that are highly conserved during evolution. In teleosts, the developing heart first jogs to the left (left-jogging) and later loops to the right (D-looping) of the embryonic midline, and the liver and pancreas are formed on the right or left sides of the body respectively. Reversals of normal L-R asymmetry occur in some zebrafish mutants and rarely in humans, a condition known as heterotaxia. Here we describe transpositions in the L-R pattern of internal organ asymmetry during Astyanax cavefish development. Imaging and immunostaining indicated that the developing hearts of surface fish embryos show left jogging and D-looping, just as in other teleosts. Surprisingly, however, a significant portion of cavefish embryos show altered heart polarity: some individuals show cardiac right-jogging and Left (L)-looping, others show no cardiac jogging or looping, and still others show the conventional cardiac left-jogging and Dlooping. Furthermore, in situ hybridization using the cystathionine ß synthase a (cbsa) gene as a marker of the developing liver and pancreas showed that these organs are positioned on the right and left sides of the midline respectively in surface fish embryos, but L-R polarity of liver and pancreas development is also reversed in a significant proportion of cavefish embryos. The results suggest that L-R asymmetry of ancestral surface fish has been modified during cavefish evolution, which is the first example to our knowledge of an evolutionary change of L-R patterning in a vertebrate. We will describe ongoing studies aimed to determine the genetic basis of modified L-R axis symmetry in cavefish, beginning with the deposition of maternal factors in eggs, proceeding through the formation of the L-R organizer in gastrulating zygotes, and ending with the execution of the Nodal-Lefty-Pitx2 signaling axis in the LPM. We will also evaluate possible evolutionary forces responsible for modifying L-R axial asymmetry in cavefish. Our results indicate that Astyanax cavefish will be an excellent model system to study the evolution of organ asymmetry and the molecular mechanisms underlying heterotaxia.

1

Astyanax Interrnational Meeting