Left–Right Specification in the Embryonic and Larval Development of Amphibians
Biomolecules in living organisms, such as amino acids and double-stranded DNA, show left–right asymmetry. Even unicellular organisms, such as ciliates, have species-specific left- or right-handedness. Such molecular chiral asymmetry and cellular left–right asymmetry have likely provided a basis for the evolution of genetically determined left–right asymmetry of organ situs and the morphology of the heart, visceral organs, and central nervous system in eumetazoans. To study left–right asymmetry of the body plan, we believe that Xenopus laevis is a valuable model organism. The early Xenopus larva forms a transparent epidermis in the ventral abdominal region; thus organ development and morphology can be easily observed without dissection.
Genetic cascades involved in left–right specification during the phylotypic somite stage are conserved among vertebrates. Key left-handed genes such as nodal, lefty, and pitx2 have been cloned and functionally characterized in Xenopus embryos. Here, we review advances over the last two decades of molecular embryology research on left–right specification in visceral organs. Despite this extensive research, Xenopus brain laterality is still elusive. This is partially explained by a lack of useful molecular markers showing left- or right-handed expression in the embryonic or larval brain in Xenopus, although in teleosts such as zebrafish, medaka, and flounder, several genes—including nodal, lefty, pitx2, otx5, and leftover—show temporary left- or right-handed expression in the epithalamic region. Prominent morphological left–right differences in the dorsal diencephalic habenular nuclei have been described in both anuran species (except for Xenopus) and urodelan species since the early twentieth century. Accordingly, it is necessary to establish a new model organism to shed light on brain laterality in amphibians.
KeywordsLaterality nodal otx5 leftover Anura Urodela Tadpole Habenula Spiracle Brain asymmetry
- Berg DA, Kirkham M, Beljajeva A, Knapp D, Habermann B, Ryge J, Tanaka EM, Simon A (2010) Efficient regeneration by activation of neurogenesis in homeostatically quiescent regions of the adult vertebrate brain. Development 137(24):4127–4134; Erratum in: Development 138(1):180PubMedCrossRefGoogle Scholar
- Concha ML, Russell C, Regan JC, Tawk M, Sidi S, Gilmour DT, Kapsimali M, Sumoy L, Goldstone K, Amaya E, Kimelman D, Nicolson T, Gründer S, Gomperts M, Clarke JD, Wilson SW (2003) Local tissue interactions across the dorsal midline of the forebrain establish CNS laterality. Neuron 39(3):423–438PubMedCrossRefGoogle Scholar
- Hojo M, Takashima S, Kobayashi D, Sumeragi A, Shimada A, Tsukahara T, Yokoi H, Narita T, Jindo T, Kage T, Kitagawa T, Kimura T, Sekimizu K, Miyake A, Setiamarga D, Murakami R, Tsuda S, Ooki S, Kakihara K, Naruse K, Takeda H (2007) Right-elevated expression of charon is regulated by fluid flow in medaka Kupffer’s vesicle. Develop Growth Differ 49(5):395–405CrossRefGoogle Scholar
- Hüsken U, Stickney HL, Gestri G, Bianco IH, Faro A, Young RM, Roussigne M, Hawkins TA, Beretta CA, Brinkmann I, Paolini A, Jacinto R, Albadri S, Dreosti E, Tsalavouta M, Schwarz Q, Cavodeassi F, Barth AK, Wen L, Zhang B, Blader P, Yaksi E, Poggi L, Zigman M, Lin S, Wilson SW, Carl M (2014) Tcf7l2 is required for left-right asymmetric differentiation of habenular neurons. Curr Biol 24(19):2217–2227PubMedPubMedCentralCrossRefGoogle Scholar
- Kawasumi A, Nakamura T, Iwai N, Yashiro K, Saijoh Y, Belo JA, Shiratori H, Hamada H (2011) Left-right asymmetry in the level of active Nodal protein produced in the node is translated into left-right asymmetry in the lateral plate of mouse embryos. Dev Biol 353(2):321–330PubMedPubMedCentralCrossRefGoogle Scholar
- Matsui M (1996) 「両生類の進化」(Evolution of the Amphibia (natural history)). Tokyo University Press, Tokyo, pp 58–64 (in Japanese)Google Scholar
- McDiarmid RW, Altig R (1999) Tadpoles: the biology of anuran larvae, 1st edn. University of Chicago Press, Chicago, pp 31–33Google Scholar
- Meno C, Ito Y, Saijoh Y, Matsuda Y, Tashiro K, Kuhara S, Hamada H (1997) Two closely-related left-right asymmetrically expressed genes, lefty-1 and lefty-2: their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryos. Genes Cells 2:513–524PubMedCrossRefGoogle Scholar
- Morgan M (1991) The asymmetrical genetic determination of laterality: flatfish, frog and human handedness. In: Bock FR, Marsh J (eds) Biological asymmetry and handedness, Ciba Foundation Symposium,162. Wiley, Chichester, pp 234–250Google Scholar
- Norris DP, Brennan J, Bikoff EK, Robertson EJ (2002) The Foxh1-dependent autoregulatory enhancer controls the level of Nodal signals in the mouse embryo. Development 129:3455–3468Google Scholar
- Onai T, Yu JK, Blitz IL, Cho KW, Holland LZ (2010) Opposing Nodal/Vg1 and BMP signals mediate axial patterning in embryos of the basal chordate amphioxus. Dev Biol 344(1):377–389; Erratum in: Dev Biol 2011. 352(1):179Google Scholar
- Toyoizumi R (2005) 「両生類胚の左右性決定の分子機構の研究 –左側特異的に発現するnodal遺伝子の発現調節機構を中心として–」. Doctoral thesis, pp 189–208 (in Japanese)Google Scholar