Regulation of germline proliferation and differentiation by direct cell-cell communication: sheath cell-germline signaling

During the development and maintenance of tissues and organs, cells must decide whether, when, where and how much to proliferate. Improper regulation of cell proliferation or differentiation can lead to developmental defects and cancer. Similar control mechanisms are shared in all organisms. Using the genetically tractable C. elegans germ line as a system, we found a role for the distal-most pair of sheath cells (Sh1, see figure above from Killian and Hubbard, 2005) in the development of the germ line. This Sh1-germline signal collaborates with signaling by the Notch pathway from the distal tip cell (DTC) to the germ line to ensure robust larval progenitor accumulation.

Using our detailed knowledge of the development of a certain class of germline tumor mutants (Killian et al., 2004; Killian and Hubbard, 2005; McGovern et al., 2009), we developed an assay (see Hubbard, 2011) to identify the molecular basis for the Sh1-germline signal. This signaling is especially interesting since understanding its molecular basis will likely provide general insight into the nature of soma-germline signaling that underlies the developmental regulation of germline cell cycle progression.

While our assay has, so far, identified several important conserved pathways that influence germline development (see Project Regulation of germline proliferation and differentiation by the environment: insulin, TOR and TGFß), the key regulator from Sh1 has yet to be identified. Further analysis of the positive hits from our screens should identify the Sh1 signal. One hypothesis is that the signal from Sh1 will activate TOR in the germ line.

Relevant Publications:

Projects:

Regulation of germline proliferation and differentiation by the environment: insulin, TOR and TGFß

Germline proliferation and differentiation during aging

Stem cell dynamics: in vivo and in silico

Regulation of germline proliferation and differentiation by direct cell-cell communication: sheath cell-germline signaling