Biomedical subjects

M D Martín-Bermudo

Publications and source records attributed to M D Martín-Bermudo.

6 recordsLinked to original sources

PubMed1998

Absence of PS integrins or laminin A affects extracellular adhesion, but not intracellular assembly, of hemiadherens and neuromuscular junctions in Drosophila embryos.

We have examined the role of integrins in the formation of the cell junctions that connect muscles to epidermis (muscle attachments) and muscles to neurons (neuromuscular junctions). To this end we have analyzed muscle attachments and neuromuscular junctions ultrastructurally in single or double mutant Drosophila embryos lacking PS1 integrin (alphaPS1betaPS), PS2 integrin (alphaPS2betaPS), and/or their potential extracellular ligand laminin A. At the muscle attachments PS integrins are essential for the adhesion of hemiadherens junctions (HAJs) to extracellular matrix, but not for their intracellular link to the cytoskeleton. The PS2 integrin is only expressed in the muscles, but it is essential for the adhesion of muscle and epidermal HAJs to electron dense extracellular matrix. It is also required for adhesion of muscle HAJs to a less electron dense form of extracellular matrix, the basement membrane. The PS1 integrin is expressed in epidermal cells and can mediate adhesion of the epidermal HAJs to the basement membrane. The ligands involved in adhesion mediated by both PS integrins seem distinct because adhesion mediated by PS1 appears to require the extracellular matrix component laminin A, while adhesion mediated by PS2 integrin does not. At neuromuscular junctions the formation of functional synapses occurs normally in embryos lacking PS integrins and/or laminin A, but the extent of contact between neuronal and muscle surfaces is altered significantly. We suggest that neuromuscular contact in part requires basement membrane adhesion to the general muscle surface, and this form of adhesion is completely abolished in the absence of laminin A.

Animals↗

PubMed1998

Neurotactin functions in concert with other identified CAMs in growth cone guidance in Drosophila.

We have isolated and characterized mutations in Drosophila neurotactin, a gene that encodes a cell adhesion protein widely expressed during neural development. Analysis of both loss and gain of gene function conditions during embryonic and postembryonic development revealed specific requirements for neurotactin during axon outgrowth, fasciculation, and guidance. Furthermore, embryos of some double mutant combinations of neurotactin and other genes encoding adhesion/signaling molecules, including neuroglian, derailed, and kekkon1, displayed phenotypic synergy. This result provides evidence for functional cooperativity in vivo between the adhesion and signaling pathways controlled by neurotactin and the other three genes.

Alleles↗

PubMed1995

Neurogenic genes control gene expression at the transcriptional level in early neurogenesis and in mesectoderm specification.

The development of the central nervous system in the Drosophila embryo is initiated by the acquisition of neural potential by clusters of ectodermal cells, promoted by the activity of proneural genes. Proneural gene function is antagonized by neurogenic genes, resulting in the realization of the neural potential in a single cell per cluster. To analyse the relationship between proneural and neurogenic genes, we have studied, in specific proneural clusters and neuroblasts of wild-type and neurogenic mutants embryos, the expression at the RNA and protein levels of lethal of scute, the most important known proneural gene in central neurogenesis. We find that the restriction of lethal of scute expression that accompanies the restriction of the neural potential to the delaminating neuroblast is regulated at the transcriptional level by neurogenic genes. These genes, however, do not control the size of proneural clusters. Moreover, available antibodies do not provide evidence for an hypothetical posttranscriptional regulation of proneural proteins by neurogenic genes. We also find that neurogenic genes are required for the specification of the mesectoderm. This has been shown for neuralized and Notch, and could also be the case for Delta and for the Enhancer of split gene complex. Neurogenic genes would control at the transcriptional level the repression of proneural genes and the activation of single-minded in the anlage of the mesectoderm.

Animals↗

PubMed1993

Molecular characterization of the lethal of scute genetic function.

The lethal of scute (l'sc) genetic function, which plays an essential role in the early development of the central nervous system of the Drosophila embryo, is localized within the achaete-scute complex (AS-C). Several lines of evidence have suggested that the AS-C T3 transcription unit corresponds to the l'sc function. We demonstrate that short fragments of DNA, containing the T3 transcribed region and a few kilobases of flanking sequences, rescue, albeit partially, the lethality and neural phenotype of l'sc deletions. Still, the complex wild-type pattern of expression of T3 is not reproduced by the transduced genes. This depends on cis-control elements scattered within the entire AS-C DNA and intermingled with regulatory elements specific for other AS-C transcription units. These elements are necessary for the initial activation of T3 in the neuroectoderm, probably mediated by axis-patterning genes. The presence of a cluster of E-boxes, upstream of the T3 transcribed region, suggests another level of control of T3 expression by basic-helix-loop-helix proteins, among them its own gene product.

Amino Acid Sequence↗

PubMed1993

Integrins and morphogenesis.

The Drosophila position specific (PS) integrins consist of two cell surface heterodimers, PS1 (alpha PS1 beta PS) and PS2 (alpha OS2 beta PS), which are expressed on complementary sides of attachments between cell layers and are essential for these attachments. Current evidence suggests that the PS integrins bind to components of the extracellular matrix, similar to the majority of vertebrate integrins, but specific Drosophila ligands have not yet been identified. In the embryo PS1 is found on the surface of the epidermis and endoderm, while PS2 is restricted to the mesoderm. The integrins are concentrated at the sites where the somatic muscles attach to the epidermis and at the interface between the visceral mesoderm and the endoderm. In myospheroid mutant embryos, which lack the beta PS subunit, the adhesion between the mesoderm and the other cell layers fails. The PS integrins are also required for the adhesion of the dorsal to the ventral surface of the wing during metamorphosis. PS1 is expressed on the basal surface of the dorsal cells and PS2 is expressed on the ventral cells. Loss of PS integrin function in the wing results in balloon shaped wings because of the failure of the two surfaces of the wing blade to adhere to each other. These and other aspects of the phenotypes of mutations in the genes encoding the PS integrins indicate that integrins play an important role in the adhesion of different cell layers to each other and thus an essential role in the morphogenesis of the organism. The use of extracellular matrix receptors in this role may aid in keeping the different cell layers distinct.

Animals↗

PubMed1991

Distribution and function of the lethal of scute gene product during early neurogenesis in Drosophila.

Genes of the achaete-scute complex (ASC) participate in the formation of the central nervous system in the Drosophila embryo. Previous genetic analyses have indicated that lethal of scute (l'sc) is the most important gene of the complex in that process. We have obtained antibodies against the l'sc protein to study the expression of the gene during early neurogenesis. The protein is found in groups of embryonic neuroectodermal cells, analogous to the proneural clusters that precede the appearance of precursors of peripheral sensory organs in imaginal epithelia. The groups appear in different regions of the neuroectoderm, accompanying the three successive waves of neuroblast segregation. Most neuroblasts delaminate from these clusters and express position-specific levels of l'sc protein. No significant differences have been found between the distribution of l'sc RNA and protein. Phenotypic analysis of a l'sc deficiency has shown that the gene is required for neuroblast commitment, although this requirement is less widespread than the domain of l'sc expression, suggesting a high degree of redundancy in the function of genes that participate in the process of neuroblast segregation. The ASC genes have been postulated to play a role in the control of NB identity, revealed by the generation of a defined lineage of identifiable neurons. However, our study in l'sc mutants of the expression of fushi tarazu, engrailed, and even-skipped, used as markers of neuronal identity, has not provided evidence to support this hypothesis.

Animals↗