Sensory perception

The series of events required for an organism to receive a sensory stimulus, convert it to a molecular signal, and recognize and characterize the signal. This is a neurological process.

RTK/Ras/MAPK signaling pathway

Receptor Tyrosine Kinase (RTK)/Ras GTPase/MAP kinase (MAPK) activated signaling pathways are used repeatedly during metazoan development to control many different biological processes. C. elegans contains two different RTKs (LET-23/EGFR and EGL-15 /FGFR) that are known to stimulate LET-60/Ras and a MAPK cascade consisting of the kinases LIN-45/Raf, MEK-2/MEK and MPK-1/ERK. This Ras/MAPK cascade is required for multiple developmental events, including induction of vulval, uterine, spicule, P12 and excretory duct cell fates, control of sex myoblast migration and axon guidance, and promotion of germline meiosis. Studies in C. elegans have provided much insight into the basic framework of this RTK/Ras/MAPK signaling pathway, its regulation, how it elicits cell-type specific responses, and how it interacts with other signaling pathways such as the Wnt and Notch pathways.

Hedgehog signaling

A conserved regulatory cascade that is important in vertebrates and Drosophila for patterning and cell proliferation during development. The main components in this pathway are Hedgehog (Hh), mammalian Sonic hedgehog (Shh), skinny hedgehog (Ski), dispatched (Disp), patched (Ptch), and Smoothened (Smo). C. elegans lacks true Hh and Smo orthologs; however, it does have orthologs of Ski, Disp, and Ptch along with multiple hegdgehog-related (Hh-r), Patched (PTC) and patched-related (PTR) genes.

Molting

Under good conditions, C. elegans enters and exits four larval stages before becoming a fertile adult. Each developmental stage is punctuated with a molt that entails the shedding of the larval cuticle and the generation of a completely new one. It has been shown that each cuticle is unique in its composition. Molting is a carefully timed process that needs to be coordinated with development, new cuticle synthesis, and cuticle shedding. Mutations in a set of genes called heterochronic genes regulates the timing development and the molts and result in precocious or retarded development of parts of the animals that aren't synchronized with the animals' life stage.

RNA processing

After transcription in the nucleus and before translation into a protein in the cytoplasm, newly transcribed RNA undergoes post-transcriptional modifications to become the mature mRNA. These modifications include the addition of a 5'cap and 3'poly A tail, and splicing out of noncoding introns. These modifications are needed for the RNA molecule to be protected against RNase activity as well as for it to be recognized by molecules that mediate translation into proteins. Splicing of the RNA is required to remove the portions of the message that are not supposed to be translated into the final protein product. In addition to intron and exon splicing of the pre-mRNA, ~70% of pre-mRNAs in C. elegans are trans-spliced to one of two different splice leader sequences, SL1 or SL2.

Cell migration

Cell movement is an essential cell behavior for metazoan development. When this process is improperly orchestrated it can result in developmental disorders or pathologies such as tumor metastasis. In C. elegans, many cell types including canal associated neurons (CANs), hermaphrodite-specific neurons (HSNs), and Q neuroblasts migrate long distances during embryonic or larval development. Studies in C. elegans have elucidated many of the molecules required for stimulating and guiding the cell. These studies have shown that some directed movement rely on graded chemotactic signaling that is perceived by the cell and transduced to the cell's cytoskeleton. Chemotactic signaling molecules such as UNC-6, an extracellular matrix protein, can act as both an attractant, for cells expressing UNC-5, or as a repellant, for cells expressing UNC-40. Cell migration ultimately requires the regulation of cytoskeletal rearrangements. Studies have demonstrated UNC-73/Trio to be a main activator of Rac signaling in at least some of these migrating cells, which is proposed to drive such intracellular changes.

Gene silencing

Inactivation of gene expression can occur at both the level of transcription and post-transcription. All silencing mechanisms are identical in that they require a small RNA species to provide the necessary gene sequence specificity and effector molecules that bind to the RNAs to process the RNA and to direct its inhibitory activity. Studies of these mechanisms in C. elegans has elucidated a number of different RNA-mediated post-transcriptional mechanisms. These mechanisms differ in the species of small RNAs involved. The different classes of small RNAs in C. elegans includes, microRNAs (miRNA), small interfering RNAs (siRNAs or rasi's), X-chromosome cluster RNAs (X-cluster), tiny noncoding RNAs (tncRNAs), and Piwi-associated RNAs (piRNAs). Gene silencing is accepted as a defense mechanism that evolved to protect the host from exogenous (foreign) sequence such as viral and transposon sequence. It has also been shown that gene silencing plays a critical role in endogenous gene expression to control the developmental timing of genes require for cell specificity, as well as playing a role in aging.

Vulval development

The C. elegans vulva connects the hermaphrodite uterus to the outside of the nematode. The development of this organ is an intensively studied biological process making it a useful model for animal organogenesis. C. elegans vulval development involves the temporal and spatial coordination of intercellular signaling, evolutionarily conserved signal transduction pathways, and transcriptional regulation. Among the pathways involved in vulval development are the WNT, epidermal growth factor (EGF), and LIN-12/NOTCH signaling pathways. These pathways work in temporal succession to prime epidermal cells to first be competent to take on vulva cell fates and later to solidify their vulval cell specification. These pathways also work antagonistically to specify the precise pattern of cell fates needed to form the vulva. A key cell in vulval development is the anchor cell. Signals from this cell initiate the transition from epidermal to vulval precursor cell. This cell also influences the specification of surrounding uterine cells, which is required to connect the uterus to the vulva. The development of the final vulval organ requires the anchor cell to invade between terminally differentiated vulval cells in a behavior analogous to that of metastatic tumor cells.

EGF signaling pathway

The Epidermal Growth Factor (EGF) signaling pathway was initially identified by Nobel Prize winner Stanley Cohen who found EGF to be involved in numerous cellular signaling events in mouse development. The single C. elegans EGF ligand, lin-3 and its receptor, lin-28 were initially found in screens for vulval development mutants. Further analysis of similar mutants, led to the identification of the C. elegans core EGFR signaling pathway components, SEM-5/GRB2, SOS-1, LET-60/RAS, LIN-45/RAF, MEK-2/MEK, and MPK-1. Positive regulators of this pathway were subsequently found in suppressor screens, and include KSR-1, SUR-8/SOC-2, and SUR-6. Negative modulators were found in further forward and reverse genetic screens and include UNC-101, SLI-1, GAP-1, SUR-5 and ARK-1 (in conjunction with GRB-2). LIN-3/EGF acts as a signal from the single anchor cell to induce neighboring undifferentiated epithelial cells to adopt the vulval fate during larval development. Impairing this signaling event results in a failure of vulval fate specification, and eventually a vulvaless animal that cannot lay eggs (the "bag of worms" phenotype). As in the mouse, EGF signaling was found to be involved in a number of other processes, although perhaps most importantly it is required for larval survival; homozygous let-23 null worms die at the L1 stage. Further, EGF signaling has been shown to function in coordinating vulva to uterus communication during development, promoting male spicule development, inducing P12.p cell fate in the epithelia, at the same time acting as a physiological signal, promoting ovulatory contractions of the gonad sheath cells, inducing a reversible nervous system quiescence during each larval molt, and regulating protein and calcium homeostasis in the adult worm.