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Sonic Hedgehog (Shh) signaling is characterized by non-cell autonomy; cells expressing Shh do not respond to the ligand. Here, we identify several Shh mutations that can activate the Hedgehog (Hh) pathway cell-autonomously. Cell-autonomous pathway activation requires the extracellular cysteine rich domain of Smoothened, but is otherwise independent of the Shh receptors Patched1 and -2. Many of the Shh mutants that gain activity fail to undergo auto processing resulting in the perdurance of the Shh pro-peptide, a form of Shh that is sufficient to activate the Hh response cell-autonomously. Our results demonstrate that Shh is capable of activating the Hh pathway via Smoothened, independently of Patched1/2, and that it harbors an intrinsic mechanism that prevents cell-autonomous activation of the Shh response.
This article was published in the following journal.
Name: Mechanisms of development
Odontogenic keratocysts (OKCs) are common cystic lesions of odontogenic epithelial origin that can occur sporadically or in association with naevoid basal cell carcinoma syndrome (NBCCS). OKCs are loc...
The term cell competition has been used to describe the phenomenon where particular cells can be eliminated during tissue growth only when more competitive cells are available to replace them. Multipl...
Adenylyl cyclases are key points for the integration of stimulatory and inhibitory G protein-coupled receptor (GPCR) signals. Adenylyl cyclase type 5 (AC5) is highly expressed in striatal medium spiny...
Cell type-specific modifications of conventional endosomal trafficking pathways lead to the formation of lysosome-related organelles (LROs). C. elegans gut granules are intestinally restricted LROs th...
The G-protein coupled receptor 37-like 1 (Gpr37l1) is specifically expressed in most astrocytic glial cells, including cerebellar Bergmann astrocytes and interacts with patched 1 (Ptch1), a co-recepto...
A preliminary clinical trial of ACTIVATE will be conducted in a sample of children with ADHD. ACTIVATE is a computerized neurocognitive training program (ACTIVATE; see: www.c8sciences.com)...
This study will evaluate the use of nivolumab before surgery in patients with high-risk clear cell renal cell carcinoma who are eligible for nephrectomy. Nivolumab is an antibody that may ...
A three months, double-blind, randomised, parallel-group study evaluating the efficacy of sitagliptin (Januvia™) versus placebo on beta-cell function in patients with newly detected gluc...
Small body size at birth, slow weight gain during infancy and increase in body mass index after 2 years are independent risk factors for cardiovascular disease and the metabolic syndrome. ...
This is a Phase 1, interventional, non-randomized, experimental infection model study with healthy adult males adults (N=32) between the ages of 18-36 at study enrollment. The study is des...
A family of calcium-independent cell adhesion molecules of the immunoglobulin superfamily. They are expressed by most cell types and mediate both homotypic and heterotypic cell-cell adhesion. Nectins function in a variety of morphogenetic and developmental processes that include organogenesis of the eye, ear, tooth, and cerebral cortex; they also play roles in viral infection and cell proliferation.
A mutation that results in an increase in a gene's activity or in acquiring a new molecular function or a new pattern of gene expression.
Genes whose loss of function or gain of function MUTATION leads to the death of the carrier prior to maturity. They may be essential genes (GENES, ESSENTIAL) required for viability, or genes which cause a block of function of an essential gene at a time when the essential gene function is required for viability.
Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.
The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.