Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 260

Cell-cell signaling serves as a common mechanism for establishing cell fate in animal development. In this scenario, signals are transmitted at specific stages of development or at particular phases of the cell lineage, resulting in the selection of a precise fate for a particular cell. It is also possible for a cell to detect multiple cues from its extracellular environment and thus the cell should be capable of discerning which signals it should initially respond to. Certain developmental changes in animals are strongly linked to specific stages of the cell cycle, whereas others are not. It is therefore essential that the target cell is cognizant of various temporal cues in order to appropriately progress through its developmental process.

One of the most extensively studied components of C. elegans is the Wnt signaling pathway that primarily controls development, either by maintaining cell renewal or allowing differentiation of stem cells. Wnt glycoproteins have the capability of binding to transmembrane protein receptors known as Frizzled. Niches in the C. elegans gonad thus possess Wnt gradients that regulate the number of stem cells that proliferate and differentiate within the gonad. Investigations using C. elegans have provided information on how a niche cell is generated. Distal tip cells are produced when a pair of somatic cells serving as gonad precursors undergo asymmetric cell division. Each precursor cell goes through this particular type of division according to the distal-proximal organizational axis; the daughter cells of the distal end thus generate more distal tip cells. Experiments involving mutations that affect this form of asymmetric cell division result in the disruption of its cellular organization, wherein both daughter cells become members of the proximal end of the gonad. Previous reports have described axis-related mutations in the genes pop-1, sys-3, and β-catenin, which are members of the Wnt signaling pathway that acts as the regulatory component of cells responsible for maintaining the distal-proximal organizational axis. Other earlier studies have shown that mutations in the mes-1 gene result in the unequal division of C. elegans stem cells, which results in a loss of polarity based on the distal-proximal axis, ultimately resulting in the cell differentiation.

C. elegans has also served as a model organism for studies involving cell induction mechanisms other than the Wnt signaling pathway. Studies indicate that extracellular signals serve as cues for precursor cells to develop into their specific fates. For example, the HOM-C transcription factors mab-5 and lin-39 are differentially expressed along the anteroposterior axis of vulval precursor cells of C. elegans, resulting in the development of the vulva. Mutation and induction assays have shown that these two transcription factors work in an antagonistic fashion that allows or prevents vulval precursor cells to act in response to neighboring anchor cells of the nematode gonad. Fibroblast growth factor and its corresponding receptor also play major roles in the establishment of the organization axis of vulval precursor cells.

The subsequent differentiation of these precursor cells results in myoblasts or muscle cells that assist in the egg-laying process of C. elegans. Pumilio (PUF) proteins pertain to a conserved family of RNA-binding proteins that regulate the translation, maintenance, and localization of various target messenger RNAs (mRNAs). A wide range of PUF proteins are involved in the development and maintenance of the C. elegans germline. For example, FBF-1 and FBF-2 are PUF proteins that are responsible in sex determination in the nematode. By inhibiting the activity of the protein fem-3, FBF-1 and FBF-2 assist in the determination whether the germ cells would proceed toward spermatogenesis or oogenesis, thus establishing the sex of the organism. On the other hand, PUF-5/6/7 pertains to another PUF protein complex that regulates the production of oocytes.