How was the notochord born?

Abstract

More than 550 million years ago, chordates originated from a common ancestor shared with nonchordate deuterostomes by developing a novel type of larva, the "tadpole larva." The notochord is the supporting organ of the larval tail and the most prominent feature of chordates; indeed, phylum Chordata is named after this organ. In this review, we discuss the molecular mechanisms involved in the formation of the notochord over the course of chordate evolution with a special emphasis on a member of T-box gene family, Brachyury. Comparison of the decoded genome of a unicellular choanoflagellate with the genomes of sponge and cnidarians suggests that T-box gene family arose at the time of the evolution of multicellular animals. Gastrulation is a morphogenetic movement that is essential for the formation of two- or three-germ-layered embryos. Brachyury is transiently expressed in the blastopore (bp) region, where it confers on cells the ability to undergo invagination. This process is involved in the formation of the archenteron in all metazoans. This is a "primary" function of Brachyury. During the evolution of chordates, Brachyury gained an additional expression domain at the dorsal midline region of the bp. In this new expression domain, Brachyury served its "secondary" function, recruiting another set of target genes to form a dorsal axial organ, notochord. The Wnt/β-catenin, BMP/Nodal, and FGF-signaling pathways are involved in the transcriptional activation of Brachyury. We discuss the molecular mechanisms of Brachyury secondary function in the context of the dorsal-ventral (D-V) inversion theory and the aboral-dorsalization hypothesis. Although the scope of this review requires some degree of oversimplification of Brachyury function, it is beneficial to facilitate studies on the notochord formation, a central evolutionary developmental biology problem in the history of metazoan evolution, pointed out first by Alexander Kowalevsky.

The Mammalian Cervical Vertebrae Blueprint Depends on theT(brachyury) Gene

“…The T gene belongs to the family of T-box genes that encode transcription factors consisting of transcriptional activator and/or repressor domains and a DNA-binding T-box domain in many eukaryotic species including vertebrates and invertebrates (Satoh et al 2012). The T protein is essential for development of the notochord and mesoderm formation in the primitive streak during early embryonic vertebrate development .…”

“…The murine brachyury (T) gene with its mutant alleles was the first gene that was identified and positionally cloned based on a genetic defect only, the long-known brachyury resulting in vertebral and spinal defects (Dobrovolskaia-Zavadskaia 1927;Herrmann et al 1990). Numerous subsequent studies confirmed that the coordinated expression of the T gene during gastrulation is essential for appropriate notochord, neural tube, and mesoderm development (Chesley 1935;Pennimpede et al 2012;Satoh et al 2012). Recently, the T gene has gained interest because of its association with the human chordoma, a sporadic and hereditary tumor originating from relicts of the notochord (Yang et al 2009;Pillay et al 2012;Nibu et al 2013).…”

The chordate ancestor possessed a single copy of the Brachyury gene for notochord acquisition

“…The organ that best characterizes chordates is the notochord, an organ that supports the beating of the muscular tail of fish-like larvae or adults [1, 3, 4]. The T-box family transcription-factor gene, Brachyury , plays an essential role in notochord formation [5]. In ascidians (urochordates), for example, Brachyury is expressed exclusively in primordial embryonic notochord cells [6, 7].…”

“…Interestingly, Brachyury is not specific to chordates, but is present in most metazoans, including non-chordate deuterostomes [5, 10]. Beside paralogs derived from ancient whole genome duplication (referred to as “ohnologs”), Brachyury is usually present as a single copy, with some exceptions ( Hydra [11], calcisponge [12], and cephalochordates (see below)), and is expressed around the blastopore during gastrulation.…”

“…We proposed an evolutionary scenario for Brachyury emphasizing its primary and secondary expression domains and functions [5]. Namely, ambulacrarians require Brachyury in its primary domain of expression and function associated with the blastopore (PEF), while chordates employ the gene, not only for PEF, but also for the secondary domain of expression and function associated with the notochord (SEF).…”