An overview of factors influencing sex determination and gonadal development in birds

The morphological development of the embryonic gonads is very similar in birds and mammals, and recent evidence suggests that the genes involved in this process are conserved between these classes of vertebrates. The genetic mechanism by which sex is determined in birds remains to be elucidated, although recent studies have reinforced the contention that steroids may play an important role in the structural development of the testes and ovaries in birds. So far, few genes have been assigned to the avian sex chromosomes, but it is known that the Z and W chromosomes do not share significant homology with the mammalian X and Y chromosomes. The commercial importance of poultry breeding has motivated considerable investment in developing physical and genetic maps of the chicken genome. These efforts, in combination with modern molecular approaches to analyzing gene expression, should help to elucidate the sex-determining mechanism in birds in the near future.     

Whatever happened to SRY?

The mammalian sex-determining gene, SRY, was identified by positional cloning approximately 10 years ago. Since its discovery, intense research into this gene has been directed on two main fronts: elucidation of its function in development of the testis and examination of its singular evolutionary history. The role or SRY as the testis-determining factor (TDF) places it at a crucial point in the highly conserved morphogenetic process of vertebrate gonadogenesis. None of the genes that directly activate SRY nor any of its immediate downstream targets have yet been positively identified. Several genes, however, such as SF1, DAX1, and SOX9, whose spatial and temporal expression profiles overlap with that of SRY, are strongly implicated as co-regulators of gonadogenesis. Molecular genetic manipulation of these genes in mice has shown that they are indispensable to sexual development. Remarkably, its key position in this cascade of gene action has not protected SRY from strong yet poorly understood selective forces that have caused it to evolve rapidly in mammals. The evolution of SRY has been characterized not only by rapid sequence divergence within mammals, but also by structural changes such as intron insertion, gene amplification, and deletion.     

The genetic and evolutionary basis of colour variation in vertebrates

Variation in pigmentation is one of the most conspicuous phenotypic traits in vertebrates. Although mammals show less variation in body pigmentation than other vertebrate groups, the genetics of colour determination and variation is best understood for them. More than 150 genes have been identified that influence pigmentation, and in many cases, the cause for variation in pigmentation has been identified down to the underlying nucleotide changes. These studies show that while some genes are often responsible for deviating pigmentation, similar or almost identical phenotypes even in the same species may be due to mutations in different genes. In this review we will first discuss the current knowledge about the genes and their functions underlying the biochemical pathways that determine pigmentation and then give examples where the mutations responsible for colour variation have been determined. Finally, we will discuss potential evolutionary causes for and consequences of differences in pigmentation between individuals.     

On the existence of cytokines in invertebrates

Based on the assumption that invertebrates, like vertebrates, possess factors regulating responses to infection or wounding, studies dealing with the evolution of immunity have focussed on the isolation and characterisation of putative cytokine-related molecules from invertebrates. Until recently, most of our knowledge of cytokine- and cytokine receptor-like molecules in invertebrates relies on functional assays and similarities at the physicochemical level. As such, a phylogenetic relationship between invertebrate cytokine-like molecules and vertebrate counterparts could not be convincingly demonstrated. Recent genomic sequence analyses of interleukin-1-receptor-related molecules, that is Toll-like receptors, and members of the transforming growth factor-β superfamily suggest that the innate immune system of invertebrates and vertebrates evolved independently. In addition, data from protochordates and annelids suggest that invertebrate cytokine-like molecules and vertebrate factors do not have the same evolutionary origin. We propose instead that the convergence of function of invertebrate cytokine-like molecules and vertebrate counterparts involved in innate immune defences may be based on similar lectin-like activities. Received 27 November 2000; received after revision 11 December 2000; accepted 13 December 2000     

Left–right asymmetry in zebrafish

In vertebrates, internal organs are positioned asymmetrically across the left-right (LR) axis, placing them in a defined area within the body. This LR asymmetric placement is a conserved feature of the vertebrate body plan. Events determining LR asymmetry occur during embryonic development, and are regulated by the coordinated action of genetic mechanisms that are evolutionarily conserved among vertebrates. Recent studies using zebrafish have provided new insights into how the Kupffer's vesicle organizer region is generated, and how it relays LR asymmetry information to the lateral plate mesoderm. In this review, we summarize recent advances in zebrafish and describe our current understanding of the mechanisms underlying these processes.     

Unique gene structure and paralogy define the 7D-cadherin family

Cadherins are Ca²⁺-dependent transmembrane glycoproteins crucial for cell-cell adhesion in vertebrates and invertebrates. Classification of this superfamily due to their phylogenetic relationship is currently restricted to three major subfamilies: classical, desmosomal and protocadherins. Here we report evidence for a common phylogenetic origin of the kidney-specific Ksp- (Cdh16) and the intestine-specific LI-cadherin (Cdh17). Both genes consist of 18 exons and the positions of their exon-intron boundaries as well as their intron phases are perfectly conserved. We found an extensive paralogy of more than 40 megabases in mammals as well as teleost fish species encompassing the Ksp- and LI-cadherin genes. A comparable paralogy was not detected for other cadherin gene loci. These findings suggest that the Ksp- and LI-cadherin genes originated by chromosomal duplication early during vertebrate evolution and support our assumption that both proteins are paralogues within a separate cadherin family that we have termed 7D-cadherins. Received 16 January 2006; received after revision 18 April 2006; accepted 11 May 2006     

Nodal signals pattern vertebrate embryos

Vertebrate embryonic patterning requires several conserved inductive signals–including Nodal, Bmp, Wnt and Fgf signals. Nodal, which is a member of the transforming growth factor β (TGFβ) superfamily, activates a signal transduction pathway that is similar to that of other TGFβ members. Nodal genes, which have been identified in numerous vertebrate species, are expressed in specific cell types and tissues during embryonic development. Nodal signal transduction has been shown to play a pivotal role in inducing and patterning mesoderm and endoderm, and in regulating neurogenesis and left-right axis asymmetry. Antagonists, which act at different steps in the Nodal signal transduction pathway, have been shown to tightly modulate the inductive activity of Nodal. Received 20 October 2005; received after revision 15 November 2005; accepted 25 November 2005     

Evolutionary diversification of the mammalian defensins

Defensins are cysteine-rich cationic peptides that function in antimicrobial defense in both invertebrates and vertebrates. Three main groups of animal defensins are known: insect defensins; mammalian alpha-defensins and vertebrate beta-defensins. It has been difficult to determine whether these molecules are homologous or have independently evolved similar features, but overall the evidence favors a distant relationship. The best evidence of this relationship is structural, particularly from their overall three-dimensional structure and from the spacing of half-cystine residues involved in intra-chain disulfide bonds. Some evidence favors a closer relationship between vertebrate beta-defensins and insect defensins than between the two groups of vertebrate defensins. Examination of nucleotide substitutions between recently duplicated mammalian defensin genes shows that the rate of nonsynonymous (amino-acid-altering) substitution exceeds that of synonymous substitution in the region of the gene encoding the mature defensin. This highly unusual pattern of nucleotide substitution is evidence that natural selection has acted to diversify defensins at the amino acid level. The resulting rapid evolution explains why it is difficult to reconstruct the evolutionary history of these molecules.     

Sex determination in mammals — Before and after the evolution of SRY

Therian mammals (marsupials and placentals) have an XX female: XY male sex chromosome system, which is homologous to autosomes in other vertebrates. The testis-determining gene, SRY, is conserved on the Y throughout therians, but is absent in other vertebrates, suggesting that the mammal system evolved about 310 million years ago (MYA). However, recent work on the basal monotreme mammals has completely changed our conception of how and when this change occurred. Platypus and echidna lack SRY, and the therian X and Y are represented by autosomes, implying that SRY evolved in therians after their divergence from monotremes only 166 MYA. Clues to the ancestral mechanism usurped by SRY in therians are provided by the monotremes, whose sex chromosomes are homologous to the ZW of birds. This suggests that the therian X and Y, and the SRY gene, evolved from an ancient bird-like sex chromosome system which predates the divergence of mammals and reptiles 310 MYA. Received 4 March 2008; received after revision 22 April 2008; accepted 3 June 2008     

Regulation of mitochondrial dynamics: convergences and divergences between yeast and vertebrates

In eukaryotic cells, the shape of mitochondria can be tuned to various physiological conditions by a balance of fusion and fission processes termed mitochondrial dynamics. Mitochondrial dynamics controls not only the morphology but also the function of mitochondria, and therefore is crucial in many aspects of a cell’s life. Consequently, dysfunction of mitochondrial dynamics has been implicated in a variety of human diseases including cancer. Several proteins important for mitochondrial fusion and fission have been discovered over the past decade. However, there is emerging evidence that there are as yet unidentified proteins important for these processes and that the fusion/fission machinery is not completely conserved between yeast and vertebrates. The recent characterization of several mammalian proteins important for the process that were not conserved in yeast, may indicate that the molecular mechanisms regulating and controlling the morphology and function of mitochondria are more elaborate and complex in vertebrates. This difference could possibly be a consequence of different needs in the different cell types of multicellular organisms. Here, we review recent advances in the field of mitochondrial dynamics. We highlight and discuss the mechanisms regulating recruitment of cytosolic Drp1 to the mitochondrial outer membrane by Fis1, Mff, and MIEF1 in mammals and the divergences in regulation of mitochondrial dynamics between yeast and vertebrates.     

Sex linkage of malic enzyme in Xenopus laevis

Genetic analysis of mME variants (mitochondrial malic enzyme, E.C. 1.1.1.40) in Xenopus laevis revealed sex linkage of the mMe locus and indicated a WZ/ZZ type of sex determination. Codominant mMe alleles occur on both W and Z chromosomes, with a recombination frequency of 6.1% +/- 1.5% between mMe and the sex-determining locus (or region).     

Heat shock protein gene expression during embryonic development of the zebrafish

Heat shock genes exhibit complex patterns of spatial and temporal regulation during embryonic development of a wide range of organisms. Our laboratory has been involved in an analysis of heat shock gene expression in the zebrafish, a model system which is now utilized extensively for the examination of early embryonic development of vertebrates. Members of the zebrafish hsp47, hsp70 and hsp90 gene families have been cloned and shown to be closely related to their counterparts in higher vertebrates. Expression of these genes has been examined using Northern blot and whole mount in situ hybridization analyses. Both the hsp47 and hsp90 genes are expressed in a highly tissue-restricted manner during normal development. The data raise a number of interesting questions regarding the function and regulation of these heat shock genes during early zebrafish development.     

Amphibian sex determination and sex reversal

Amphibians employ a genetic mechanism of sex determination, according to all available information on sex chromosomes or breeding tests. Sex reversal allows breeding tests to establish which sex is heterogametic and provides an indication of the mechanism of sex determination. Cases of spontaneous and experimental sex reversal (by temperature, hormones or surgery) are reviewed and illustrated by previously unpublished studies on crested newts. These newts respond conventionally to temperature and hormone treatment but provide anomalous results from breeding tests. It is suggested that both the evolution from temperature dependency to a genetic switch and from ZZ/ZW to XX/XY are superimposed on a generally uniform mechanism of sex determination in all vertebrates.     

Sex linkage of malic enzyme inXenopus laevis

Genetic analysis of mME variants (mitochondrial malic enzyme, E.C. 1.1.1.40) inXenopus laevis revealed sex linkage of the mMe locus and indicated a WZ/ZZ type of sex determination. Codominant mMe alleles occur on both W and Z chromosomes, with a recombination frequency of 6.1%±1.5% between mMe and the sex-determining locus (or region).     

Autophagy: molecular mechanisms,physiological functions and relevance in human pathology

Autophagy is a degradative mechanism mainly involved in the recycling and turnover of cytoplasmic constituents from eukaryotic cells. Over the last years, yeast genetic screens have considerably increased our knowledge about the molecular mechanisms of autophagy, and a number of genes involved in fundamental steps of the autophagic pathway have been identified. Most of these autophagy genes are present in higher eukaryotes indicating that this process has been evolutionarily conserved. In yeast, autophagy is mainly involved in adaptation to starvation, but in multicellular organisms this route has emerged as a multifunctional pathway involved in a variety of additional processes such as programmed cell death, removal of damaged organelles and development of different tissue-specific functions. Furthermore, autophagy is associated with a growing number of pathological conditions, including cancer, myopathies and neurodegenerative disorders. The physiological and pathological roles of autophagy, as well as the molecular mechanisms underlying this multifunctional pathway, are discussed in this review.Received 12 January 2004; received after revision 29 January 2004; accepted 4 February 2004     

Insights into acylphosphatase structure and catalytic mechanism

Acylphosphatase is one of the smallest enzymes known (about 98 amino acid residues). It is present in organs and tissues of vertebrate species as two isoenzymes sharing over 55% of sequence homology; these appear highly conserved in differing species. The two isoenzymes can be involved in a number of physiological processes, though their effective biological function is not still certain. The solution and crystal structures of different isoenzymes are known, revealing a close packed protein with a fold similar to that shown by other phosphate-bind ing proteins. The structural data, together with an extended site-directed mutagenesis investigation, led to the identification of the residues involved in enzyme catalysis. However, it appears unlikely that these residues are able to perform the full catalytic cycle: a substrate-assisted catalytic mechanism has therefore been proposed, in which the phosphate moiety of the substrate could act as a nucleophile activating the catalytic water molecule. Received 12 November 1996; accepted 27 November 1996     

Soluble factors and the development of rod photoreceptors

Photoreceptors are the most abundant cell type in the vertebrate neural retina. Like the other retinal neurons and the Müller glia, they arise from a population of precursor cells that are multipotent and intrinsic to the retina. Approximately 10 years ago, several studies demonstrated that retinal precursor cells (RPCs) are competent to respond to environmental factors that promote cell type determination and differentiation. Since those studies, significant effort has been directed at identifying the molecular nature of these environmental signals and understanding the precise mechanisms they employ to drive RPCs towards the different retinal fates. In this review, we describe the recent progress toward understanding how environmental factors influence the development of vertebrate rod photoreceptors.     

An ancient cytokine,astakine, mediates circadian regulation of invertebrate hematopoiesis

Invertebrate circulating hemocytes are key players in the innate immune defense and their continuous renewal from hematopoietic tissues is tightly regulated in crustaceans by astakine, a new family of cytokines sharing a prokineticin (PROK) domain. In vertebrates, brain PROKs function as transmitters of circadian rhythms and we present evidence that hemocyte release from hematopoietic tissues in crayfish is under circadian regulation, a direct result of rhythmic expression of astakine. We demonstrate that the observed variation in astakine expression has an impact on innate immunity assessed as susceptibility to a pathogenic Pseudomonas species. These findings enlighten the importance of comparing immune responses at fixed times not to neglect circadian regulation of innate immunity. Moreover, our results entail an evolutionary conserved function for prokineticins as mediators of circadian rhythm, and for the first time show a role for this domain in circadian regulation of hematopoiesis that may have implications also in vertebrates.