Gene duplications in early metazoan evolution

Major increases in complexity during animal evolution occurred at the transition from a unicellular protozoan to a multicellular metazoan, the evolution of Bilateria from diploblasts (possibly the Cambrian explosion) and during early vertebrate evolution. A role for gene duplication in the third event has been widely discussed. Here I examine the possible role of gene duplications and domain shuffling in the first two events. There is evidence for a wave of gene duplications and shuffling which may have paved the way for multicellularity; there are also examples of gene duplications that may have facilitated the transition from diploblasts to Bilateria.     

Gene-regulatory interactions in neural crest evolution and development

In this review, we outline the gene-regulatory interactions driving neural crest development and compare these to a hypothetical network operating in the embryonic ectoderm of the cephalochordate amphioxus. While the early stages of ectodermal patterning appear conserved between amphioxus and vertebrates, later activation of neural crest-specific factors at the neural plate border appears to be a vertebrate novelty. This difference may reflect co-option of genetic pathways which conferred novel properties upon the evolving vertebrate neural plate border, potentiating the evolution of definitive neural crest.     

The early steps of neural crest development.

The neural crest is an intriguing cell population that gives rise to many derivatives which are all generated far from their final destinations. From its induction to the delamination of the cells, multiple signalling pathways converge to regulate the expression of effector genes, the products of which endow the cells with invasive and migratory properties reminiscent of those displayed by malignant cells in tumours. As such, the neural crest constitutes an excellent model to study cell migration.     

The origin and evolution of the neural crest

Many of the features that distinguish the vertebrates from other chordates are derived from the neural crest, and it has long been argued that the emergence of this multipotent embryonic population was a key innovation underpinning vertebrate evolution. More recently, however, a number of studies have suggested that the evolution of the neural crest was less sudden than previously believed. This has exposed the fact that neural crest, as evidenced by its repertoire of derivative cell types, has evolved through vertebrate evolution. In this light, attempts to derive a typological definition of neural crest, in terms of molecular signatures or networks, are unfounded. We propose a less restrictive, embryological definition of this cell type that facilitates, rather than precludes, investigating the evolution of neural crest. While the evolutionary origin of neural crest has attracted much attention, its subsequent evolution has received almost no attention and yet it is more readily open to experimental investigation and has greater relevance to understanding vertebrate evolution. Finally, we provide a brief outline of how the evolutionary emergence of neural crest potentiality may have proceeded, and how it may be investigated.     

Growth factor synergism and antagonism in early neural crest development.

This review article focuses on data that reveal the importance of synergistic and antagonistic effects in growth factor action during the early phases of neural crest development. Growth factors act in concert in different cell lineages and in several aspects of neural crest cell development, including survival, proliferation, and differentiation. Stem cell factor (SCF) is a survival factor for the neural crest stem cell. Its action is neutralized by neurotrophins, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) through apoptotic cell death. In contrast, SCF alone does not support the survival of melanogenic cells (pigment cell precursors). They require the additional presence of a neurotrophin (NGF, BDNF, or NT-3). Fibroblast growth factor-2 (FGF-2) is an important promoter of proliferation in neuronal progenitor cells. In neural crest cells, fibroblast growth factor treatment alone does not lead to cell expansion but also requires the presence of a neurotrophin. The proliferative stimulus of the fibroblast growth factor - neurotrophin combination is antagonized by transforming growth factor beta-1 (TGFbeta-1). Moreover, TGFbeta-1 promotes the concomitant expression of neuronal markers from two cell lineages, sympathetic neurons and primary sensory neurons, indicating that it acts on a pluripotent neuronal progenitor cell. Moreover, the combination of FGF-2 and NT3, but not other neurotrophins, promotes expression or activation of one of the earliest markers expressed by presumptive sympathetic neuroblasts, the norepinephrine transporter. Taken together, these data emphasize the importance of the concerted action of growth factors in neural crest development at different levels and in several cell lineages. The underlying mechanisms involve growth-factor-induced dependence of the cells on other factors and susceptibility to growth-factor-mediated apoptosis.     

The neural crest in vertebrate evolution

Vertebrates belong to the group of chordates characterized by a dorsal neural tube and an anteroposterior axis, the notochord. They are the only chordates to possess an embryonic and pluripotent structure associated with their neural primordium, the neural crest (NC). The NC is at the origin of multiple cell types and plays a major role in the construction of the head, which has been an important asset in the evolutionary success of vertebrates. We discuss here the contribution of the rostral domain of the NC to craniofacial skeletogenesis. Moreover, recent data show that cephalic NC cells regulate the activity of secondary brain organizers, hence being critical for preotic brain development, a role that had not been suspected before.     

Gene duplications: the gradual evolution of functional divergence

Budding yeast provides a useful resource for studies of gene function. A new analysis of the fitness effects of deletion mutations in budding yeast reveals that genes that have duplicates create lower fitness losses when inactivated than do genes that are singletons.     

Gene duplications in the structural evolution of chymotrypsin.

Chymotrypsin and other members of the serine protease enzyme family have a structure built from two similar domains, each of which is a hydrogen-bonded barrel, containing six antiparallel strands of beta-sheet bonded in the order ABCFED-A …. The folding patterns of the domains have been re-examined by several newly improved shape comparison methods to see whether the barrels could have evolved by gene duplication, as proposed by Matthews and Blow (Birktoft &; Blow, 1972). The domains have a similar hydrogen-bond pattern, the same shear number (defined in this paper) for the twist of the barrel, and the cores of their β-sheets can be superimposed so that 46 topologically equivalent α-carbons fit within a root-mean-square distance of 2.43 Å and a larger set of 57 α-carbons fit within 3.4 Å. These results are highly significant when judged against shape comparisons of many other proteins with themselves, and give strong evidence for gene duplication. The duplication does not include any SS bridges.Both domains have a surprisingly symmetrical structure of two halves ABC, DEF paired round a dyad axis, and the half-domains are each made of two loops twisted in an L-shape, since the second strand (B or E) is bent into two halves B₁, B₂ or E₁, E₂. The cores of the four half-domains, each of 23 α-carbons, superimpose in pairs with root-mean-square distances ranging from 1.79 to 2.45 Å. In the entire molecule the half-domains are related by a screw dyad which converts domain I strands (ABC) (DEF) into domain II strands (DEF) (ABC) superimposing the six strands with a root-mean-square distance of 2.35 Å. These observations suggest that the Chymotrypsin barrel originally evolved from a closely-linked dimer of two intertwined half-domains which became united into one. domain by gene duplication. The enzyme evolved from a second dimer of two full domains and a second duplication. The bacterial protease B from Streptomyces griseus shows the same structural repeats and is consistent with the gene duplication hypothesis.Improved methods for shape comparison of proteins have been developed which are very fast and reliable.     

Development and evolution of the neural crest: an overview

The neural crest is a multipotent and migratory cell type that forms transiently in the developing vertebrate embryo. These cells emerge from the central nervous system, migrate extensively and give rise to diverse cell lineages including melanocytes, craniofacial cartilage and bone, peripheral and enteric neurons and glia, and smooth muscle. A vertebrate innovation, the gene regulatory network underlying neural crest formation appears to be highly conserved, even to the base of vertebrates. Here, we present an overview of important concepts in the neural crest field dating from its discovery 150 years ago to open questions that will motivate future research.     

Molecular regulation of neural crest development

The neural crest is a transient embryonic structure that gives rise to a multitude of different cell types in the vertebrate. As such, it is an iideal model to study the processes of vertebrate differentiation and development. This review focuses on two major questionsrelated to neural crest development. The first question concerns the degree and time of commitment of the neural crest cellsto differntt cell lineages and the emerging role of the homebox containing genes in regulating this process. Evidence from the cephalic crest suggests that the commitment process does start before the neural crest cells migrate away from the neural tube and gene ablation experiments suggest that different homeobox genes are required for the development of neural and mesenchymal tissue derivatives. However, clonal analysis of neural crest cell before migration suggests that many of the cells remain multi-potential indicating that the final determinative steps occur progressively during migration and in association with environmental influences. The second question concerns the nature of the environmental factors that determine the differentiation of neural crest cells into discrete lineages. Evidence is provided, mainly from in vitro experiments, that purified growth factors selectively promote the differentiation of neural crest cells down either sympathetic, adrenal, sensory, or melanocytic cell lineages.     

Epigenetic regulation in neural crest development

The neural crest (NC) is a multipotent, migratory cell population that arises from the developing dorsal neural fold of vertebrate embryos. Once their fates are specified, neural crest cells (NCCs) migrate along defined routes and differentiate into a variety of tissues, including bone and cartilage of the craniofacial skeleton, peripheral neurons, glia, pigment cells, endocrine cells, and mesenchymal precursor cells (Santagati and Rijli,2003; Dupin et al.,2006; Hall,2009). Abnormal development of NCCs causes a number of human diseases, including ear abnormalities (including deafness), heart anomalies, neuroblastomas, and mandibulofacial dysostosis (Hall,2009). For more than a century, NCCs have attracted the attention of geneticists and developmental biologists for their stem cell-like properties, including self-renewal and multipotent differentiation potential. However, we have only begun to understand the underlying mechanisms responsible for their formation and behavior. Recent studies have demonstrated that epigenetic regulation plays important roles in NC development. In this review, we focused on some of the most recent findings on chromatin-mediated mechanisms for vertebrate NCC development.