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POP-1 controls axis formation during early gonadogenesis in C. elegans

¹ Laboratory of Genetics,
² Department of Biochemistry,
³ Laboratory of Molecular Biology, and
⁴ Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI 53706-1544 USA

View larger version (37K): [in a new window]   Fig. 1. Early gonadogenesis in wild-type and Sys mutant animals. See Kimble and Hirsh (Kimble and Hirsh, 1979) for more detail about wild type and see Miskowski et al. (Miskowski et al., 2001) for more detail about sys-1 mutants. (A) The gonadal primordium is morphologically indistinguishable in hermaphrodites and males (primordium symmetry represented by arrows beneath figure). The somatic gonadal precursors, Z1 and Z4, reside at the poles of the primordium; germline precursors, Z2 and Z3 (not shown), reside centrally between Z1 and Z4. (B) Z1 and Z4 divide asymmetrically in both sexes. When first born, their daughters are positioned with the same symmetry as the earlier primordium (arrows point towards proximal regions). In hermaphrodites, this symmetry is retained throughout gonadogenesis. (C) In males, the Z1/Z4 daughters rearrange (left figure, curved arrows) to generate an asymmetric structure (right figure, single arrow points towards proximal pole). (D) Fates of Z1/Z4 daughters in wild-type hermaphrodites. Z1.a and Z4.p give rise to DTCs (red), which have leader function and control germline proliferation. Z1.p and Z4.a give rise to AC/VU cells. Lateral signaling results in selection of one precursor as an AC (dark blue) and the other as a ventral uterine precursor (VU), one of nine somatic gonadal blast cells (light blue) that form the somatic gonadal primordium in hermaphrodites (SPh). gl, germline. (E) Fates of Z1/Z4 daughters in wild-type males (and most sys-1 mutant males). Z1.a and Z4.p give rise to DTCs (blue), which control germline proliferation, but do not have leader function. Z1.p and Z4.a give rise to cells with potential to become either a linker cell (LC) or a vas deferens blast cell (VD). Lateral signaling results in selection of one of these precursors as an LC (red), which has leader function; the other becomes a VD, one of seven somatic gonadal blast cells (light blue) that form the somatic gonadal primordium (SPm). gl, germ line. (F) Fates of Z1/Z4 daughters in sys-1 mutant hermaphrodites. All four Z1/Z4 daughters can give rise to AC/VU cells, and no DTCs are made. Furthermore, no SPh forms; instead, a ring of somatic gonadal cells encircles the germline (gl) at late L2/early L3. (G) Fates of Z1/Z4 daughters in 30% of sys-1 mutant males. Z1 and Z4 do not make DTCs; instead extra LCs and extra somatic gonadal cells are observed by late L2.

View larger version (45K): [in a new window]   Fig. 2. Molecular basis of pop-1(Sys) mutations. (A) Diagram of POP-1 protein. A ß-catenin binding domain resides at the N terminus (blue) and an HMG DNA binding domain is located centrally (red). Sites of pop-1(Sys) lesions are marked. (B) pop-1(q645) is predicted to change a conserved aspartic acid (D) to glutamic acid (E) in the ß-catenin binding domain. (C) pop-1(q624) is predicted to change a conserved asparagine (N) to isoleucine (I) in the HMG box. Each alignment includes human LEF-1 (hlef-1), murine TCF-4 (mtcf-4), Xenopus TCF-3 (xtcf-3), Drosophila Pangolin (pan), and C. elegans POP-1.

View larger version (65K): [in a new window]   Fig. 3. Defects in pop-1(Sys) hermaphrodite gonad. (A-C) Animals carrying lag-2::GFP. Animals in A and C carry qIs56[lag-2::GFP], animal in B carries qIs19[lag-2::GFP]. Both transgenes have similar GFP expression in the DTC, but qIs56 has brighter GFP expression in the ventral nerve cord than qIs19. (A) Wild-type L3, SPh and one gonadal arm are shown. The DTC caps the end of the elongating arm and expresses lag-2::GFP brightly (arrow). Somatic gonadal cells within the SPh (black arrowheads) cluster centrally. (B,C) pop-1(q645) and pop-1(RNAi) animals have no gonadal elongation and no bright lag-2::GFP expression. Somatic gonadal cells are arranged around the gonadal periphery (black arrowheads). (D-F) Animals expressing cdh-3::GFP. (D) Wild-type L3. The AC marker cdh-3::GFP is expressed in a single cell (white arrowhead). (E,F) pop-1(q645) and pop-1(RNAi) L3 animals can have multiple ACs (white arrowheads).

View larger version (18K): [in a new window]   Fig. 4. Early lineage of Z1 or Z4 in wild-type and pop-1 defective animals. (A-D) Vertical lines represent cells; horizontal lines represent divisions. Z1/Z4 represents Z1 or Z4; left daughter is distal; right daughter is proximal. DTC, distal tip cell; AC/VU, anchor cell or ventral uterine precursor; LC/VD, linker cell or vas deferens precursor. Only cell divisions in L1 and L2 were observed. (A) Wild-type hermaphrodite. The distal daughter divides once and gives rise to a DTC; the proximal daughter divides twice and gives rise to an AC/VU. (B) pop-1(q645). Two hermaphrodites were watched from hatching until L2 lethargus. Z1/Z4 distal daughters divided twice, in three out of four cases; no DTCs were made. (C) Wild-type male. The distal daughter does not divide and becomes a DTC; the proximal daughter divides twice and gives rise to an LC/VD. (D) pop-1(RNAi) male. Z1/Z4 distal daughters both migrated anteriorly and divided once, albeit later than their proximal sisters. Later divisions were not followed.

View larger version (104K): [in a new window]   Fig. 5. Defects in pop-1(Sys) and pop-1(RNAi) male gonads. All animals carry qIs56[lag-2::GFP], which expresses brightly in the LC and weakly in DTCs and other somatic gonadal cells. LC, linker cell; SPm, somatic primordium of male; DTC, distal tip cell. Extents of SPm and germline are indicated by brackets. (A,B) Wild-type L2 male. Single LC leads migration of the single gonadal arm. The SPm resides directly behind the LC and follows its migration. Two DTCs are present, but only one is seen in this focal plane (arrowhead). (C,D) pop-1(q645) male in L2 lethargus or early L3. Two LCs are present. The SPm appears normal: the somatic gonadal cells cluster to the anterior and follow the migrating LC. Only one DTC is present (arrowhead). (E,F) pop-1(RNAi) L2 male. Gonad polarity and organization are normal: the SPm is established at the anterior directly behind the LC. However, no DTCs are present and the LC has not migrated. The lack of LC migration is accompanied by a widening of the developing gonad.

View larger version (30K): [in a new window]   Fig. 6. Models for control of Z1/Z4 asymmetry. (A) Two models by which Z1 and Z4 might be polarized. See text for explanation. (B) Pathways of POP-1 control. See text for explanation.