During the development of multicellular organisms asymmetric cell divisions are required to increase the cell numbers and generate diverse cell types. In C. elegans, as in other animals, the conserved Wnt signaling pathway controls asymmetric cell divisions and cell fate specifications. For example, in the C. elegans tail,
lin-44/Wnt and
lin-17/frizzled control the asymmetric division of the TL and TR cells (collectively referred to as T cells). In wild-type animals, POP-1, a TCF-4/LEF-1 homolog, is distributed asymmetrically to the nuclei of the T cell daughters: the anterior daughter, T.a, has a higher level of POP-1 than does the posterior daughter, T.p. Mutations in
lin-44cause a reversal of T cell polarity and a corresponding reversal in the level of POP-1: T.a has a lower level of POP-1 and T.p. has a higher level. Mutations in
lin-17 cause a loss of T cell polarity and equally high level of POP-1 in both T.a and T.p. This suggests that
pop-1 is downstream of
lin-44 and
lin-17. We have isolated several mutations defining the new genes that interact with
lin-44 and
lin-17 in the control of asymmetric division of the T cell. One of these is
tcl-2 (T cell lineage defective). Cell lineage analysis has revealed that
tcl-2 mutations cause defects in the pattern and asymmetry of the T cell divisions. Furthermore, both T.a and T.p had equally high levels of POP-1 in
tcl-2 mutants, as we observed in
lin-17 mutants, suggesting that
tcl-2 also functions before
pop-1 in the control of the T cell division. We cloned
tcl-2 by transformation rescue and found sequence changes in four sequenced
tcl-2 mutant alleles. No related proteins have been found in a variety of database searches, suggesting that
tcl-2 encodes a novel protein. A
tcl-2::gfptranslational fusion construct rescued the T cell division defect and was weakly expressed in the nuclei of the T cells and certain T cell descendants. In addition, we found that
tcl-2mutants also have defects in the development of gonadal axes and the specification of the P11/P12 cell fate, both of which involve the Wnt signaling pathway. Double mutant analyses revealed that
tcl-2 acts synergistically with
lin-44 and
lin-17 in the control of gonad development and P11/P12 cell fate specification. A role for LIN-44 in the development of the gonadal axes was unexpected, as neither
lin-44 nor any other C. elegans Wnt gene has been shown to be involved in gonad development. Our data suggest that
tcl-2 may either act in a parallel pathway or to modulate the Wnt signaling pathway in the control of the asymmetric T cell divisions, gonad development and P11/P12 fate specification.