Molecular characterization of nervous system organization in the hemichordate acorn worm Saccoglossus kowalevskii.

Hemichordates are an important group for investigating the evolution of bilaterian nervous systems. As the closest chordate outgroup with a bilaterally symmetric adult body plan, hemichordates are particularly informative for exploring the origins of chordates. Despite the importance of hemichordate neuroanatomy for testing hypotheses on deuterostome and chordate evolution, adult hemichordate nervous systems have not been comprehensively described using molecular techniques, and classic histological descriptions disagree on basic aspects of nervous system organization.

Anteroposterior axis patterning by early canonical Wnt signaling during hemichordate development.

The Wnt family of secreted proteins has been proposed to play a conserved role in early specification of the bilaterian anteroposterior (A/P) axis. This hypothesis is based predominantly on data from vertebrate embryogenesis as well as planarian regeneration and homeostasis, indicating that canonical Wnt (cWnt) signaling endows cells with positional information along the A/P axis. Outside of these phyla, there is strong support for a conserved role of cWnt signaling in the repression of anterior fates, but little comparative support for a conserved role in promotion of posterior fates.

On the Relationship of Protein and mRNA Dynamics in Vertebrate Embryonic Development.

A biochemical explanation of development from the fertilized egg to the adult requires an understanding of the proteins and RNAs expressed over time during embryogenesis. We present a comprehensive characterization of protein and mRNA dynamics across early development in Xenopus. Surprisingly, we find that most protein levels change little and duplicated genes are expressed similarly.

The deuterostome context of chordate origins.

Our understanding of vertebrate origins is powerfully informed by comparative morphology, embryology and genomics of chordates, hemichordates and echinoderms, which together make up the deuterostome clade. Striking body-plan differences among these phyla have historically hindered the identification of ancestral morphological features, but recent progress in molecular genetics and embryology has revealed deep similarities in body-axis formation and organization across deuterostomes, at stages before morphological differences develop. These developmental genetic features, along with robust support of pharyngeal gill slits as a shared deuterostome character, provide the foundation for the emergence of chordates.

On a possible evolutionary link of the stomochord of hemichordates to pharyngeal organs of chordates.

As a group closely related to chordates, hemichordate acorn worms are in a key phylogenic position for addressing hypotheses of chordate origins. The stomochord of acorn worms is an anterior outgrowth of the pharynx endoderm into the proboscis. In 1886 Bateson proposed homology of this organ to the chordate notochord, crowning this animal group "hemichordates.

The Fox/Forkhead transcription factor family of the hemichordate Saccoglossus kowalevskii.

Background: The Fox gene family is a large family of transcription factors that arose early in organismal evolution dating back to at least the common ancestor of metazoans and fungi. They are key components of many gene regulatory networks essential for embryonic development. Although much is known about the role of Fox genes during vertebrate development, comprehensive comparative studies outside vertebrates are sparse.

From feedback inhibition to allostery: the enduring example of aspartate transcarbamoylase.

Aspartate transcarbamoylase (ATCase) of Escherichia coli, the first enzyme of the pyrimidine biosynthetic pathway, is inhibited by CTP and UTP, the nucleotide end-products of the pathway. First discovered by Yates and Pardee in 1956 [Yates R & Pardee AB (1956) J Biol Chem 221, 743-756; Yates RA & Pardee AB (1956) J Biol Chem 221, 757-770], these interactions establish feedback inhibition in vivo, a key means of metabolic regulation by which end-product production by the pathway is adjusted to end-product usage in macromolecule synthesis. Activation of the enzyme by the purine nucleotide ATP may also have regulatory significance.

Identical genomic organization of two hemichordate hox clusters.

Genomic comparisons of chordates, hemichordates, and echinoderms can inform hypotheses for the evolution of these strikingly different phyla from the last common deuterostome ancestor. Because hox genes play pivotal developmental roles in bilaterian animals, we analyzed the Hox complexes of two hemichordate genomes. We find that Saccoglossus kowalevskii and Ptychodera flava both possess 12-gene clusters, with mir10 between hox4 and hox5, in 550 kb and 452 kb intervals, respectively.

β-catenin specifies the endomesoderm and defines the posterior organizer of the hemichordate Saccoglossus kowalevskii.

The canonical Wnt/β-catenin pathway is a key regulator of body plan organization and axis formation in metazoans, being involved in germ layer specification, posterior growth and patterning of the anteroposterior axis. Results from animals spanning a wide phylogenetic range suggest that a unifying function of β-catenin in metazoans is to define the posterior/vegetal part of the embryo. Although the specification of vegetal territories (endoderm) by β-catenin has been demonstrated in distantly related animals (cnidarians, a protostome, echinoderms and ascidians), the definition of the posterior part of the embryo is well supported only for vertebrates and planarians.

Enzymes, embryos, and ancestors.

In the 1950s, cellular regulatory mechanisms were newly recognized; with Arthur Pardee I investigated the initial enzyme of pyrimidine biosynthesis, which he discovered is controlled by feedback inhibition. The protein proved unusual in having separate but interacting sites for substrates and regulators. Howard Schachman and I dissociated the protein into different subunits, one binding regulators and one substrates.

Co-option of an anteroposterior head axis patterning system for proximodistal patterning of appendages in early bilaterian evolution.

The enormous diversity of extant animal forms is a testament to the power of evolution, and much of this diversity has been achieved through the emergence of novel morphological traits. The origin of novel morphological traits is an extremely important issue in biology, and a frequent source of this novelty is co-option of pre-existing genetic systems for new purposes (Carroll et al., 2008).

The theory of facilitated variation.

This theory concerns the means by which animals generate phenotypic variation from genetic change. Most anatomical and physiological traits that have evolved since the Cambrian are, we propose, the result of regulatory changes in the usage of various members of a large set of conserved core components that function in development and physiology. Genetic change of the DNA sequences for regulatory elements of DNA, RNAs, and proteins leads to heritable regulatory change, which specifies new combinations of core components, operating in new amounts and states at new times and places in the animal.

The deuterostome ancestor.

Hemichordates, the phylum of bilateral animals closest to chordates, can illuminate the evolutionary origins of various chordate traits to determine whether these were already present in a shared ancestor (the deuterostome ancestor) or were evolved within the chordate line. We find that an anteroposterior map of gene expression domains, representing 42 genes of neural patterning, is closely similar in hemichordates and chordates, though it is restricted to the neural ectoderm in chordates whereas in hemichordates, which have a diffuse nervous system, it encircles the whole body. This map allows an accurate alignment of the anterioposterior axes of members of the two groups.

Dorsoventral patterning in hemichordates: insights into early chordate evolution.

We have compared the dorsoventral development of hemichordates and chordates to deduce the organization of their common ancestor, and hence to identify the evolutionary modifications of the chordate body axis after the lineages split. In the hemichordate embryo, genes encoding bone morphogenetic proteins (Bmp) 2/4 and 5/8, as well as several genes for modulators of Bmp activity, are expressed in a thin stripe of ectoderm on one midline, historically called "dorsal." On the opposite midline, the genes encoding Chordin and Anti-dorsalizing morphogenetic protein (Admp) are expressed.

Hemichordates and the origin of chordates.

Hemichordates, the phylum of bilateral animals most closely related to chordates, could reveal the evolutionary origins of chordate traits such as the nerve cord, notochord, gill slits and tail. The anteroposterior maps of gene expression domains for 38 genes of chordate neural patterning are highly similar for hemichordates and chordates, even though hemichordates have a diffuse nerve-net. About 40% of the domains are not present in protostome maps.

Anteroposterior patterning in hemichordates and the origins of the chordate nervous system.

The chordate central nervous system has been hypothesized to originate from either a dorsal centralized, or a ventral centralized, or a noncentralized nervous system of a deuterostome ancestor. In an effort to resolve these issues, we examined the hemichordate Saccoglossus kowalevskii and studied the expression of orthologs of genes that are involved in patterning the chordate central nervous system. All 22 orthologs studied are expressed in the ectoderm in an anteroposterior arrangement nearly identical to that found in chordates.

Induction of notochord by the organizer inXenopus.

One important step in understanding early development is to define the cell interactions involved in establishing tissue types. In amphibian embryos, one such interaction is the induction by the organizer region after the late blastula stage of lateral and ventral regions of the marginal zone (MZ) to form dorsal tissue types such as muscle. It is not known whether the organizer can also induce lateral MZ to form notochord after the late blastula stage.