OTUD3: A Lys6 and Lys63 specific deubiquitinase in early vertebrate development.

Ubiquitination and deubiquitylation regulate essential cellular processes and involve hundreds of sequentially acting enzymes, many of which are barely understood. OTUD3 is an evolutionarily highly conserved deubiquitinase involved in many aspects of cellular homeostasis. However, its biochemical properties and physiological role during development are poorly understood.

Cilia-localized GID/CTLH ubiquitin ligase complex regulates protein homeostasis of sonic hedgehog signaling components.

Cilia are evolutionarily conserved organelles that orchestrate a variety of signal transduction pathways, such as sonic hedgehog (SHH) signaling, during embryonic development. Our recent studies have shown that loss of GID ubiquitin ligase function results in aberrant AMP-activated protein kinase (AMPK) activation and elongated primary cilia, which suggests a functional connection to cilia. Here, we reveal that the GID complex is an integral part of the cilium required for primary cilia-dependent signal transduction and the maintenance of ciliary protein homeostasis.

Interplay of TRIM2 E3 Ubiquitin Ligase and ALIX/ESCRT Complex: Control of Developmental Plasticity During Early Neurogenesis.

Tripartite motif 2 (TRIM2) drives neurite outgrowth and polarization, is involved in axon specification, and confers neuroprotective functions during rapid ischemia. The mechanisms controlling neuronal cell fate determination and differentiation are fundamental for neural development. Here, we show that in , knockdown affects primary neurogenesis and neural progenitor cell survival.

lrpap1 as a specific marker of proximal pronephric kidney tubuli in Xenopus laevis embryos.

LRPAP1, also known as receptor associated protein (RAP) is a small protein of 40 kDa associated with six of the seven members of the evolutionary conserved family of LDL receptors. Numerous studies showed that LRPAP1 has a dual function, initially as a chaperone insuring proper formation of intermolecular disulfide bonds during biogenesis of low density lipoprotein (LDL) receptors and later as an escort protein during trafficking through the endoplasmic reticulum and the early Golgi compartment, preventing premature interaction of receptor and ligand. Because of the general influence of LRPAP1 protein on lipid metabolism, we analyzed the temporal and spatial expression of the Xenopus laevis ortholog of lrpap1.

A multichannel computer-driven system to raise aquatic embryos under selectable hypoxic conditions.

The formation of a functional cardiovascular system is an essential step in the early vertebrate embryo. Nevertheless, the effect of hypoxia on the developmental program of organisms was studied rarely. In particular, this holds true for vertebrate embryos that depend on a functional placenta for proper development and had not been studied in this respect due to the obvious limitation.

Hedgehog-dependent E3-ligase Midline1 regulates ubiquitin-mediated proteasomal degradation of Pax6 during visual system development.

Pax6 is a key transcription factor involved in eye, brain, and pancreas development. Although pax6 is expressed in the whole prospective retinal field, subsequently its expression becomes restricted to the optic cup by reciprocal transcriptional repression of pax6 and pax2 However, it remains unclear how Pax6 protein is removed from the eyestalk territory on time. Here, we report that Mid1, a member of the RBCC/TRIM E3 ligase family, which was first identified in patients with the X-chromosome-linked Opitz BBB/G (OS) syndrome, interacts with Pax6.

Suppression of vascular network formation by chronic hypoxia and prolyl-hydroxylase 2 (phd2) deficiency during vertebrate development.

In the adult, new vessels and red blood cells form in response to hypoxia. Here, the oxygen-sensing system (PHD-HIF) has recently been put into focus, since the prolyl-hydroxylase domain proteins (PHD) and hypoxia-inducible factors (HIF) are considered as potential therapeutic targets to treat ischemia, cancers or age-related macula degeneration. While the oxygen-sensing system (PHD-HIF) has been studied intensively in this respect, only little is known from developing vertebrate embryos since mutations within this pathway led to an early decease of embryos due to placental defects.

Xenopus cadherin 5 is specifically expressed in endothelial cells of the developing vascular system.

Vasculogenesis is an important, multistep process leading to the formation of a functional primary network of blood vessels in the developing embryo. A series of interactions between secreted growth factors and their specific receptors leads to the specification of mesodermal cells to become hemangioblasts, which then differentiate into angioblasts. These subsequently proliferate, coalesce into cords and finally form tubular vascular structures.

Treatment with bone morphogenetic protein 2 limits infarct size after myocardial infarction in mice.

Various strategies have been devised to reduce the clinical consequences of myocardial infarction, including acute medical care, revascularization, stem cell transplantations, and more recently, prevention of cardiomyocyte cell death. Activation of embryonic signaling pathways is a particularly interesting option to complement these strategies and to improve the functional performance and survival rate of cardiomyocytes. Here, we have concentrated on bone morphogenetic protein 2 (BMP-2), which induces ectopic formation of beating cardiomyocytes during development in the mesoderm and protects neonatal cardiomyocytes from ischemia-reperfusion injury.

Xenopus er71 is involved in vascular development.

Vasculogenesis and hematopoiesis are closely linked in developing vertebrates. Recently, the existence of a common progenitor of these two tissues, the hemangioblast, has been demonstrated in different organisms. In Xenopus early vascular and hematopoietic cells differentiate in a region called the anterior ventral blood island (aVBI).

Kidney specific expression of cTPTE during development of the chick embryo.

Here we report the cloning and expression of chick TPTE, the avian ortholog of the mammalian pTEN2 gene. In the chick embryo, cTPTE expression begins at HH (Hamburger and Hamilton) stage 18 and is restricted to the tubular structures of the developing kidney. In the mesonephros, cTPTE expression localizes to the proximal tubules.

Overexpression of Kelch domain containing-2 (mKlhdc2) inhibits differentiation and directed migration of C2C12 myoblasts.

Targeted migration of muscle precursor cells to the anlagen of limb muscles is a complex process, which is only partially understood. We have used Lbx1 mutant mice, which are unable to establish correct migration paths of muscle precursor cells into the limbs to identify new genes involved in the accurate placement of myogenic cells in developing muscles. We found that mKlhdc2 (Kelch domain containing-2), a novel member of the family of Kelch domain containing proteins, is significantly downregulated in Lbx1 homozygous mutant embryos.

Divergent siblings: E2F2 and E2F4 but not E2F1 and E2F3 induce DNA synthesis in cardiomyocytes without activation of apoptosis.

Proliferation of mammalian cardiomyocytes ceases around birth when a transition from hyperplastic to hypertrophic myocardial growth occurs. Previous studies demonstrated that directed expression of the transcription factor E2F1 induces S-phase entry in cardiomyocytes along with stimulation of programmed cell death. Here, we show that directed expression of E2F2 and E2F4 by adenovirus mediated gene transfer in neonatal cardiomyocytes induced S-phase entry but did not result in an onset of apoptosis whereas directed expression of E2F1 and E2F3 strongly evoked programmed cell death concomitant with cell cycle progression.