Biomedical subjects

Clark R Coffman

Publications and source records attributed to Clark R Coffman.

4 recordsLinked to original sources

PubMed2005

DNA damage-induced programmed cell death: potential roles in germ cell development.

The detection of DNA damage is necessary to protect against proliferation of potentially harmful cells and often results in cell cycle arrest and programmed cell death. Key components of DNA damage signaling networks include ATM, CHK2, p53, and Bax. Mutations in these damage signaling systems are linked to tumorigenesis and developmental abnormalities. Expression of some of these genes in primordial germ cells (PGCs) argues that PGCs may utilize DNA damage-induced signaling mechanisms to select against germ cells that are genetically defective, thus maintaining the integrity of the germline. This paper summarizes the roles of these DNA damage signaling molecules and addresses their potential involvement in germ cell development.

Animals↗

PubMed2005

G protein-coupled receptor roles in cell migration and cell death decisions.

Recognition of external conditions and the elicitation of appropriate responses are critical to a cell's ability to adjust to various developmental and environmental cues. G protein-coupled receptors (GPCRs) are a large class of receptors that act to relay external information into the cell by initiating signaling pathways that allow the cell to adapt to its present conditions. There are numerous ligands that activate GPCRs to initiate a multitude of intracellular signaling cascades involved in critical decisions including cell growth, differentiation, proliferation, migration, survival, and death. This article focuses on the signaling pathways involved in cell migration, survival, and death decisions with an emphasis on germ cells from various organisms.

Animals↗

PubMed2003

Cell migration and programmed cell death of Drosophila germ cells.

Cell migration and programmed cell death are essential components of animal development and homeostasis, and the germ cells of Drosophila provide a simple genetic system to study the molecular mechanisms that govern these important cellular processes. Detailed descriptions of germ cell migration in Drosophila were accomplished long ago, but most genetic and molecular analyses of the process have occurred within the past 10 years. A few of the genes required for germ cell migration have been identified, and a very interesting picture is emerging. However, a process as complex as cell migration must involve the functions of many more molecules. In addition, cell migration and cell death mechanisms are often linked, as it is important to eliminate cells that are misplaced and could present a danger to the organism. In Drosophila, genes involved in germ cell migration can also affect programmed cell death. Currently, very little is known about how germ cells ectopic to the gonads are eliminated. To date, only four genes have been reported with roles in germ cell death, and three of these have additional functions in germ cell pathfinding. The nature of the cell death program has not been elucidated. Here, I provide a brief review of Drosophila germ cell migration and programmed cell death at both the descriptive and molecular levels. Many questions remain to be answered, but advances made in recent years are providing useful insights into these critical biological phenomena.

Animals↗

PubMed2002

Identification of X-linked genes required for migration and programmed cell death of Drosophila melanogaster germ cells.

Drosophila germ cells form at the posterior pole of the embryo and migrate to the somatic gonad. Approximately 50% of the germ cells that form reach their target. The errant cells within the embryo undergo developmentally regulated cell death. Prior studies have identified some autosomal genes that regulate germ cell migration, but the genes that control germ cell death are not known. To identify X-linked genes required for germ cell migration and/or death, we performed a screen for mutations that disrupt these processes. Here we report the identification of scattershot and outsiders, two genes that regulate the programmed death of germ cells. The scattershot gene is defined by a mutation that disrupts both germ cell migration and the death of germ cells ectopic to the gonad. Maternal and zygotic expression of scattershot is required, but the migration and cell death functions can be genetically uncoupled. Zygotic expression of wild-type scattershot rescues germ cell pathfinding, but does not restore the programmed death of errant cells. The outsiders gene is required zygotically. In outsiders mutant embryos, the appropriate number of germ cells is incorporated into the gonad, but germ cells ectopic to the gonad persist.

Animals↗