Biomedical subjects

P Callaerts

Publications and source records attributed to P Callaerts.

7 recordsLinked to original sources

PubMed1997

Squid Pax-6 and eye development.

Pax-6 in vertebrates and its homolog eyeless in Drosophila are known to be essential for eye development. Here we investigate the role of Pax-6 in eye development in another major systematic group, molluscs. We demonstrate that alternatively spliced RNAs derived from a single Pax-6 gene in the squid (Loligo opalescens) are expressed in the embryonic eye, olfactory organ, brain, and arms. Despite significant sequence differences between squid Pax-6 and Drosophila eyeless in the region outside the paired- and homeodomains, squid Pax-6 is able to induce the formation of ectopic eyes in Drosophila. Our results support the idea that Pax-6 related genes are necessary for eye and olfactory system formation throughout the animal kingdom.

Amino Acid Sequence↗

PubMed1997

PAX-6 in development and evolution.

Pax-6 is a member of the Pax gene class and encodes a protein containing a paired domain and a homeodomain. The molecular characterization of Pax-6 genes from species of different animal phyla and the analysis of Pax-6 function in the developing eyes and central nervous system of vertebrates, Drosophila melanogaster, and Caenorhabditis elegans suggest that Pax-6 homologues share conserved functions. In this review, we present recent data on the structural and functional characterization of Pax-6 homologues from species of different animal phyla. We discuss the implications of these findings for our understanding of the development and evolution of eyes and nervous systems.

Animals↗

PubMed1997

Conservation of Pax-6 in a lower chordate, the ascidian Phallusia mammillata.

The Pax-6 genes of vertebrates and invertebrates encode transcription factors with both a paired domain and a homeodomain. They are expressed in the developing eye and in the central nervous system. Loss-of-function mutations in mammals and in flies result in a reduction or absence of eyes and targeted expression of the Drosophila and the mouse Pax-6 genes induces ectopic eye structures in Drosophila. These findings lead to the proposal that the morphogenesis of the different types of eyes is controlled by a Pax-6-dependent genetic pathway and that the various eye types are of monophyletic origin. We have isolated a Pax-6 homologous gene from the ascidian Phallusia mammillata, because ascidians occupy an important position in early chordate evolution. Furthermore, the Phallusia larva has a simple photosensitive ocellus. Phallusia Pax-6 shares extensive sequence identity and conserved genomic organization with the known Pax-6 genes of vertebrates and invertebrates. Expression of Phallusia Pax-6 is first detected at late gastrula stages in distinct regions of the developing neural plate. At the tailbud stage, it is expressed in the spinal cord and the brain vesicle, where the sensory organs (ocellus and otolith) form, suggesting an important function in their development. Ectopic expression of the ascidian Pax-6 gene in Drosophila leads to the induction of supernumerary eyes indicating a highly conserved gene regulatory function for Pax-6 genes.

Amino Acid Sequence↗

PubMed1995

Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila.

The Drosophila gene eyeless (ey) encodes a transcription factor with both a paired domain and a homeodomain. It is homologous to the mouse Small eye (Pax-6) gene and to the Aniridia gene in humans. These genes share extensive sequence identity, the position of three intron splice sites is conserved, and these genes are expressed similarly in the developing nervous system and in the eye during morphogenesis. Loss-of-function mutations in both the insect and in the mammalian genes have been shown to lead to a reduction or absence of eye structures, which suggests that ey functions in eye morphogenesis. By targeted expression of the ey complementary DNA in various imaginal disc primordia of Drosophila, ectopic eye structures were induced on the wings, the legs, and on the antennae. The ectopic eyes appeared morphologically normal and consisted of groups of fully differentiated ommatidia with a complete set of photoreceptor cells. These results support the proposition that ey is the master control gene for eye morphogenesis. Because homologous genes are present in vertebrates, ascidians, insects, cephalopods, and nemerteans, ey may function as a master control gene throughout the metazoa.

Animals↗

PubMed1995

New perspectives on eye evolution.

The highly complex eyes of vertebrates, insects and molluscs have long been considered to be of independent evolutionary origin. Recently, however, Pax-6, a highly conserved transcription factor, has been identified as a key regulator of eye development in both mammals and flies. Homologues of Pax-6 have also been identified in species from other phyla, including molluscs. The wide variety of eyes in the animal kingdom may, therefore, have evolved from a single ancestral photosensitive origin.

Animals↗

PubMed1992

Electrical-ionic control of gene expression.

1. Changes in turgor, in cell volume, in membrane potential, in intracellular ionic activities and, more recently, in spontaneous electrical activity have been reported to be causally linked to the expression of specific genes. 2. As a result, it has become clear that changes in membrane properties and/or in the intracellular "ionic environment" can play an important role in generating cell type specific physiological responses which indirectly--or maybe directly--affect gene expression. 3. Possible targets of the ionic "environment" are: the selective transport across biological membranes; the activity of certain (regulatory) enzymes; the conformation of some (regulatory) proteins; of chromatin; of the cytoskeleton; of the nuclear matrix; the association of the cytoskeleton with plasmamembrane proteins or RNA; the association chromatin-nuclear matrix; protein-DNA and protein-protein interactions etc. All these sites may be instrumental to "fine or coarse" tuning of gene expression. 4. The exact mechanisms by which changes in intracellular ionic environment are transduced, directly or indirectly, into alterations of the activity of trans-acting factors have not yet been fully uncovered. Changes in the degree of phosphorylation of regulatory proteins and/or of trans-acting factors may provoke fine tuning effects on cell type specific gene expression activity. 5. The intranuclear ionic environment is difficult to measure in an exact way. It can be influenced in a number of ways. The location of a gene, as determined by the position of the nucleus in the cytoplasm and by the association of chromatin to the nuclear matrix may be especially important in cells which can generate some type of intracellular gradient or in excitable cells. 6. In some somatic cell types--germinal vesicles may behave differently--the intranuclear inorganic ionic "environment" has been reported to be distinct from the cytoplasmic one. This challenges the widespread assumption that the nuclear envelope is always freely permeable to small molecules and inorganic ions. 7. It can be expected that the fast progress in the cloning of "electrically" controlled genes, in the identification of trans-acting factors, in their mode of interaction with genes and in the precise localization of genes within the nucleus may soon lead to substantial progress in this domain.

Animals↗

PubMed1992

The pivotal role of the plasma membrane-cytoskeletal complex and of epithelium formation in differentiation in animals.

1. If a few exceptions are disregarded, the several somatic cell types of a differentiated organism all have an identical genome. They all differ in their plasma membrane-cytoskeletal complex. 2. Differences in plasma membrane properties usually result in differences in ionic concentrations/activities in the cytoplasm and nucleoplasm. A basic question therefore is whether there exists a causal relationship between the ionic environment of the nucleus and differential gene expression/protein synthesis. 3. Development is switched on by a "Ca2+ explosion", often accompanied by pH changes and plasma membrane depolarisation. The penetration of the spermatozoon in the plasma membrane acts as a trigger. 4. All animal species develop from a blastula. At this stage they organise themselves as an epithelium enclosing an inner (fluid) compartment. This suggests that epithelium formation is absolutely essential in animal development. 5. As development proceeds, more and more compartments, lined by different epithelia, are formed. Differentiated organisms largely consist of folded epithelia. Some cells leave their original epithelial environment and become free floating (e.g. blood cells) or engage in other types of organisation. 6. Epithelial cells have the ability to segregate some membrane proteins, e.g. receptors, ion pumps, ion channels etc., so as to make selective transcellular transport possible. The cytoskeleton plays an important role in this segregation and in the interconnection of epithelial cells. 7. Transembryonic electric currents which have been measured by the vibrating probe technique, are due to electrogenic ion transport by epithelia. 8. Segregation of membrane proteins is not an exclusive property of epithelial cells but it is probably a property of all animal cell types, single cells inclusive; asymmetry is the rule, symmetry--if it exists at all--the exception. 9. Differences in several plasma membrane proteins (receptors, ion transporting molecules, cell adhesion molecules and signal transducing systems) are not only causally related to differential transcellular transport but also indirectly to differential protein synthesis and hence to differentiation. There are already a few well documented examples of "electrical" control of gene expression. 10. The major "strategy" which applies in differentiation seems to be to keep the genome constant but to change over and over its ionic and macromolecular environment, both acting in a complementary way. The first one may be considered as the coarse tuning mechanism of gene expression-protein synthesis, the second as the fine one. In our opinion this might be a principle universal to differentiation processes in all animal species.

Animals↗