Biomedical subjects

Marijana Miljkovic-Licina

Publications and source records attributed to Marijana Miljkovic-Licina.

4 recordsLinked to original sources

PubMed2006

Hydra, a niche for cell and developmental plasticity.

The silencing of genes whose expression is restricted to specific cell types and/or specific regeneration stages opens avenues to decipher the molecular control of the cellular plasticity underlying head regeneration in hydra. In this review, we highlight recent studies that identified genes involved in the immediate cytoprotective function played by gland cells after amputation; the early dedifferentiation of digestive cells into blastema-like cells during head regeneration, and the early late proliferation of neuronal progenitors required for head patterning. Hence, developmental plasticity in hydra relies on spatially restricted and timely orchestrated cellular modifications, where the functions played by stem cells remain to be characterized.

Animals↗

PubMed2006

Silencing of the hydra serine protease inhibitor Kazal1 gene mimics the human SPINK1 pancreatic phenotype.

In hydra, the endodermal epithelial cells carry out the digestive function together with the gland cells that produce zymogens and express the evolutionarily conserved gene Kazal1. To assess the hydra Kazal1 function, we silenced gene expression through double-stranded RNA feeding. A progressive Kazal1 silencing affected homeostatic conditions as evidenced by the low budding rate and the induced animal death. Concomitantly, a dramatic disorganization followed by a massive death of gland cells was observed, whereas the cytoplasm of digestive cells became highly vacuolated. The presence of mitochondria and late endosomes within those vacuoles assigned them as autophagosomes. The enhanced Kazal1 expression in regenerating tips was strongly diminished in Kazal1(-) hydra, and the amputation stress led to an immediate disorganization of the gland cells, vacuolization of the digestive cells and death after prolonged silencing. This first cellular phenotype resulting from a gene knock-down in cnidarians suggests that the Kazal1 serine-protease-inhibitor activity is required to prevent excessive autophagy in intact hydra and to exert a cytoprotective function to survive the amputation stress. Interestingly, these functions parallel the pancreatic autophagy phenotype observed upon mutation within the Kazal domain of the SPINK1 and SPINK3 genes in human and mice, respectively.

Amino Acid Sequence↗

PubMed2004

The orphan COUP-TF nuclear receptors are markers for neurogenesis from cnidarians to vertebrates.

In bilaterians, COUP-TF nuclear receptors participate in neurogenesis and/or CNS patterning. In hydra, the nervous system is formed of sensory mechanoreceptor cells (nematocytes) and neuronal cells, both lineages deriving from a common stem cell. The hydra COUP-TF gene, hyCOUP-TF, which encodes highly conserved DNA-binding and ligand-binding domains, belongs to the monophyletic COUP-TFs orphan receptor family (NR2F). In adult polyps, hyCOUP-TF is expressed in nematoblasts and a subset of neuronal cells. Comparative BrDU labeling analyses performed on cells expressing either hyCOUP-TF or the paired-like gene prdl-b showed that prdl-b expression corresponded to early stages of proliferation, while hyCOUP-TF was detected slightly later. HyCOUP-TF and prdl-b expressing cells disappeared in sf-1 mutants becoming "nerve-free". Moreover hyCOUP-TF and prdl-b expression was excluded from regions undergoing developmental processes. These data suggest that hyCOUP-TF and prdl-b belong to a genetic network that appeared together with neurogenesis during early metazoan evolution. The hyCOUP-TF protein specifically bound onto the evolutionarily conserved DR1 and DR5 response elements, and repressed transactivation induced by RAR:RXR nuclear receptors in a dose-dependent manner when expressed in mammalian cells. Hence, a cnidarian transcription factor can be active in vertebrate cells, implying that functional interactions between COUP-TF and other nuclear receptors were evolutionarily conserved.

Amino Acid Sequence↗

PubMedDate not supplied

Neuronal evolution: analysis of regulatory genes in a first-evolved nervous system, the hydra nervous system.

Cnidarians represent the first animal phylum with an organized nervous system and a complex active behavior. The hydra nervous system is formed of sensory-motoneurons, ganglia neurons and mechanoreceptor cells named nematocytes, which all differentiate from a common stem cell. The neurons are organized as a nerve net and a subset of neurons participate in a more complex structure, the nerve ring that was identified in most cnidarian species at the base of the tentacles. In order to better understand the genetic control of this neuronal network, we analysed the expression of evolutionarily conserved regulatory genes in the hydra nervous system. The Prd-class homeogene prdl-b and the nuclear orphan receptor hyCOUP-TF are expressed at strong levels in proliferating nematoblasts, a lineage where they were found repressed during patterning and morphogenesis, and at low levels in distinct subsets of neurons. Interestingly, Prd-class homeobox and COUP-TF genes are also expressed during neurogenesis in bilaterians, suggesting that mechanoreceptor and neuronal cells derive from a common ancestral cell. Moreover, the Prd-class homeobox gene prdl-a, the Antp-class homeobox gene msh, and the thrombospondin-related gene TSP1, which are expressed in distinct subset of neurons in the adult polyp, are also expressed during early budding and/or head regeneration. These data strengthen the fact that two distinct regulations, one for neurogenesis and another for patterning, already apply to these regulatory genes, a feature also identified in bilaterian related genes.

Animals↗