Loss of noggin1, a classic embryonic inducer gene, in elasmobranchs

Abstract

Secreted proteins of the Noggin family serve as pivotal regulators of early development and cell differentiation in all multicellular animals, including vertebrates. Noggin1 was identified first among all Noggins. Moreover, it was described as the first known embryonic inducer specifically secreted by the Spemann organizer and capable of inducing a secondary body axis when expressed ectopically. In the classical default model of neural induction, Noggin1 is presented as an antagonist of BMP signalling, playing a role as a neural inducer. Additionally, Noggin1 is involved in the dorsalization of embryonic mesoderm and later controls the differentiation of various tissues, including muscles, bones, and neural crest derivatives. Hitherto, noggin1 was found in all studied vertebrates. Here, we report the loss of noggin1 in elasmobranchs (sharks, rays and skates), which is a unique case among vertebrates. noggin2 and noggin4 retained in this group and studied in the embryos of the grey bamboo shark Chiloscyllium griseum revealed similarities in expression patterns and functional properties with their orthologues described in other vertebrates. The loss of noggin1 in elasmobranchs may be associated with histological features of the formation of their unique internal cartilaginous skeleton, although additional research is required to establish functional connections between these events.

Figure 1

Schematic phylogeny of Chondrichthyes with the representatives, included in Noggin analysis.

Figure 2

ML (A) and NJ (B) phylogenetic trees of vertebrate Noggin proteins. Bootstrap values > 50 are shown. Ac—Anolis carolinensis, Aca—Amia calva, Ar—Amblyraja radiata, Bf—Branchiostoma floridae, Cc—Carcharodon carcharias, Cg—Chiloscyllium griseum, Cp—Chiloscyllium punctatum, Cpl—Chiloscyllium plagiosum, Cm—Callorhinchus milii, Ci—Ciona intestinalis, Dr—Danio rerio, Eb—Eptatretus burgeri, Ec—Erpetoichthys calabaricus, Gg—Gallus gallus, Ho—Hemiscyllium ocellatum, Hs– Homo sapiens, Io—Isurus oxyrinchus, Lc—Latimeria chalumnae, Le—Leucoraja erinacea, Lo—Lepisosteus oculatus, Pa—Protopterus annectens, Pm—Petromyzon marinus, Pp—Pristis pectinata, Ps—Polypterus senegalus, Rt—Rhincodon typus, Sa—Squalus acanthias, Sc—Scyliorhinus canicula, Sk—Saccoglossus kowalevskii, St—Scyliorhinus torazame, Sti—Stegostoma tigrinum, Xl—Xenopus laevis.

Figure 3

Local genomic synteny analysis of vertebrate noggin genes.

Figure 4

Spatial expression of noggin2 (A–F) and noggin4 (G–L) in the embryos of the grey bamboo shark C. griseum. Fb forebrain, mb midbrain, hb hindbrain.

Figure 5

Sections of C. griseum embryos after noggin2 (A–E) and noggin4 (F–H) ISH. fvzc forebrain ventricular zone cells, hvzc hindbrain ventricular zone cells, mvzc midbrain ventricular zone cells. (A,B) stage 24, (C–H) stage 26.

Figure 6

C. griseum noggin2 mRNA induces the formation of additional body axes when injected into X. laevis embryos. (A,B) in high quantities (50 pg per embryo), noggin2 mRNA of C. griseum causes disruption of normal development at the neurula stage and the formation of mushroom-shaped embryos. (C–H) injections of 5 pg per embryo of C. griseum noggin2 mRNA lead to the induction of secondary body axes, including those containing full-fledged forehead structures and paired eyes. (I,J) Noggin4 does not induce secondary axes in X. laevis.