many investigators, the most intriguing genes in Drosophila melanogaster. F:r,',?? those referred to as homoeotics. In their mutant state, they transform an.
DELETION ANALYSIS OF THE TUMOROUS-HEAD ( t ~ h - 3 ) GENE IN DROSOPHILA MELANOGASTER DAVID T. KUHN, DANIEL F. W O O D S
AND
DEBORAH J. ANDREW
Department of Biological Sciences, University of Central Florida, Orlando, Florida 32816 Manuscript received November 26, 1980 Revised copy received July 17, 1981 ABSTRACT
In the presence of the naturally occurring maternal-effect alleles tuh-1” or tuh-is, the tuh-3 mutant gene can cause the tumorous-head trait or the sac-testis trait. The tuh-3 gene functions as a semidominant in the presence of the tuh-lh maternal effect. Eye-antennal structures are replaced by posterior abdominal tergites and genital structures. If tuh-lh is replaced by its naturally occurring allele tuh-lg, tuh-3 functions as a recessive hypomorph and the defect switches from anterior to posterior structures, with a male genital-disc defect appearing with variable penetrance. Function and regulation of tuh-3+ may better be understood in light of the cytological localization of tuh-3 either adjacent to or as part of the bithorax complex. The tuh-3 gene product appears to be essential for normal development, at least in the posterior end of the embryo. f
many investigators, the most intriguing genes in Drosophila melanogaster F:r,’,?? those referred to as homoeotics. I n their mutant state, they transform a n
organ or part of an organ into a tissue type normally restricted to a different part of the body. LEWIShas shown that the bithorax complex (BX-C) houses a series of such genes that have played an important role in the evolution of Drosophila from multi-legged ancestors (LEWIS1963, 1964, 1978). The BX-C is involved in the regulation of determination of the metathoracic and abdominal segments (LEWIS1978; GARCIA-BELLIDO 1977). A second cluster of homoeotic mutants in 3R, approximately 10 map units to the left of BX-C, appears to control determinative decisions in the head and prothorax and has been termed the Antennapedia complex by KAUFMAN, LEWISand WAKIMOTO (1980). As demonstrated in this study, the tumorous-head gene (tuh-3) resides close to or within the distal end of the bithorax-complex and acts as a semidominant to produce the tumorous-head phenotype; it maps between 3-58.0 and 3-58.9 (GARDNER1959; LINDSLEYand GRELL 1968; BOURNIAS-VARDIABASIS and BOWNES1978; WOOLF1968). Unless an X-linked gene (symbolized t ~ h - 1 ~is) present to produce a maternal effect, the penetrance of the trait is less than 1% (GARDNER and WOOLF1949). However, in the presence of tuh-lh, which is located at 1-65.3 (WOOLFand PASSAGE 1980), penetrance can be elevated to more than 90% (KUHN1974). PYATI(1976) localized the tuh-2 gene to sali1
Present addre;s: Thmann Laboratories, University of California, Santa C n u , California
Genetics 99: 99-107 September. 1981
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D. T. K U H N ,
D. F. WOODS A N D D.
J. ANDREW
vary chromosome bands 20A1-2. The X-linked tuh-lh maternal-effect gene is not mutant; it codes for a maternal-effect substance that is deposited during oogenesis (WOOLF and PASSAGE 1980). The mutant tuh-3 gene is activated during early embryogenesis ( GARDNER and WOOLF1949; BOURNIAS-VARDIABASIS and BOWNES 1978) and is thought to interact in some manner with the maternal-effect substance at that time. Therefore, the mutant gene acts at about the time of cellular determination. Resulting from the gene action is a variety of homoeotic alterations primarily confined to derivatives of the eye-antennal imaginal disc. The first homoeotic structures observed were leg-like appendages from the antenna (NEWBY1949). A re-examination by POSTLETHWAIT, BRYANT and SCHUBIGER(1972) revealed homoeotic abdominal tergites in tuh eyes and male genital tissue in antennal structures. In yet a more detailed analysis of the tuh homoeosis, KUHN, ZUST and ILLMENSEE (1979) found 6th abdominal tergites in eyes of tuh males and 6th, 7th and 8th tergites in tuh females. POSTLETHWAIT, BRYANTand SCHUBIGER ( 1972) reported homoeotic genital structures in males only, while KUHN,ZUST and ILLMENSEE (1979) and KUHNand DORGAN (1975) found both male and female genital structures. Except for the homoeotic legs, all homoeotic transformations are to sexually dimorphic posterior structures (KUHN, ZUST and ILLMENSEE 1979). A second effect ascribed to tuh-3 is seen when tuh-lh is replaced by a naturally occurring allele designated tuh-lg by WOOLF and PASSAGE (1980). Head abnormalities become rare and the tuh-3 gene functions as a recessive mutant causing a defect in the male genital disc (WOOLP 1966, 1968). The tuh-Ig gene is responsible for a maternal effect that produces gonadal dysgenesis and structural abnormalities in derivatives of the genital disc. Penetrance of the trait is variable, with a high of more than 60% (WOOLF1966). One limitation in studies of tuh-3 is the complexity of the system. Many naturally occurring modifying genes influence penetrance and expressivity of the tumorous-head phenotype. In addition to the interactions between tuh-l alleles (tuh-lh, tuh-lg) and tuh-3, the penetrance of the maternal effects can be drastically altered by introducing other modifiers. WOOLF and PASSAGE (1980) found that penetrance of the tuh trait could be shifted from a low of 7.4% to a high of 88% simply by varying the genetic background. To further complicate the system, a structural difference exists for chromosome 3 (WOOLFand PHELPS 1960). The tumorous-head strain used in our laboratory tuh(UCF) possesses a chromosome, designated 3A, in nThich the recessive gene hairy ( h ) was placed in 3L (WOOLF and KNOWLES1964). This strain carries tuh-3 in 3R. The homologous chromosome, referred to as 3B, may possess the Payne inversion with the recessive gene for scarlet eyes [Zn(3L)P, st] in 3L and tuh-3 in 3R (WOOLF and PHELPS 1960). It is homozygous lethal due to a recessive lethal mutation in 3L. I n tuh (UCF) a balanced lethal condition evolved (KUHN 1970) whereby flies are 3A/3B heterokaryotypes. Penetrance is quite variable between strains (WOOLF1965) and is even variable between siblings within an individual strain. KUHN (1974) and WOOLFand LOTT (1965) found penetrance higher
LOCATION OF
tuh-3 IN D.melanogaster
101
in 3A/3B than in ,3A/3A flies, with females showing higher penetrance than males. Perhaps the variability in penetrance and expressivity of the tumorous-head phenotype delayed progress on mapping the mutant tuh-3 gene. The objective of this paper is to deletion-map tuh-3 and present data supporting the sugges1965,1968) that tuh-3 causes both the tumorous-head and genital tion (WOOLF disc defects, depending on which maternal effect gene is present. MATERIALS A N D METHODS
Drosophila stocks: All flies were raised at about 25" on a standard Drosophila medium consisting of cornmeal-agar-sucrose-dried yeast-molasses, with propionic acid added as a mold inhibitor. The following stocks were used during this study. ( 1 ) tuh(UCF): a tumorous-head strain (tuh-lh; tuh-3) maintained for the past 10 years at the University of Central Florida; (2) Canton-S and Oregon-R-C wild-type strains; ( 3 ) M5; 2-3: a strain in which the tumoroushead X chromosome was replaced by a Muller-5 X chromosome carrying tuh-19 ( 2 and 3 refer to tuh chromosomes); (4) FMA3, y z / Y ; 2-3: a strain with FMA3, ys attached-X chromosomes with tuh-Is, and tumorous-head genetic background in females that were backcrossed each generation to tuh(UCF) males; (5) Df(3R)sbdl*5/LVM: one of a series of 3R deletion-bearing chromosomes tested. The (3R) designation for all deficiencies is omitted for sake of brevity and in the case of Df sbdl05, the LVM chromosome was replaced by either rucuca ( r u h th st cu sr es ca) or rucues ( T u h th st cu sr e S ) ; (6) Dp(1;3)PI15; Of PII5/TMI: a stock containing a translocation of part of 3R to the proximal tip of the X chromosome; shortened to D f PIISITMI; (7) y Dp(1,3)115; Dp scJ4 Dp bxdlOO red Df PI15 e l l / T M I , shortened to Dp bxdlOO-Df P115; ( 8 ) Df bxdlOg/TMl; ( 9 ) Df P2/T(2;3)apXa; (10) Df PIO/TMI; (11) Df Ubxlog/Xa; (12) Df PS/Dp P 5 ; (13) Df C4ISb Dp P 5 ; (14) T(I;3)bxdl1l/TMI, symbolized Df bxdlll. Proximal and distal breakpoints for most deleted regions are given, along with pertinent references, in Table 2. Df C4 and Df bzdl'l delete most of the BX-C. However, the exact limits of the deletions are not yet established (LEWIS,personal communication) and are therefore omitted from Table 2. The male offspring from crosses involving the deletion stocks were classifiable because nondeletion males were phenotypically different from deletion-bearing males. In crosses where translocations were used, the translocated chromosome 3 region was to the X chromosome. The deficient males resulted when the free female X chromosome segregates with the male Y chromosome. The sibling males possessed the nondeficient balancer TMI chromosome with the dominant mutation M i . RESULTS
Location of tuh-3 by deletion mapping: WOOLF (1966, 1968) suggested that tuh-3 acts as a recessive gene with reduced penetrance when in the presence of the tuh-ls gene. When tuh(UCF) males were mated with FMA3,y2/Y; 2-3 females, .32.3% of all male offspring possessed sac- or bean-shaped testes (Table 1). If FMA3,y8 females were not always backcrossed to tuh(UCF) males, the penetrance of the trait would drop dramatically, as seen in male offspring from M 5 ; 2-3 females that show only 0.6% penetrance (Table 1). In Canton-S and Oregon-R-C wild-type males, the sac-testis phenotype was not observed. Both wild-type strains carry the tuh-Ig allele. With tuh-3 acting as a simple recessive gene in the presence of tuh-jg, the deletion mapping of tuh-3 was unambigous (Table 1). Dfsbd105,Df bxd"', Df
102
D. T. KUHN, D. F. WOODS A N D D. J. A N D R E W
TABLE 1 Mapping of tuh-3 in the presence of the sac-testis maiernal effect gene (tuh-16) in aneuploids
dd
Matings (XI
PP
iuh-3/tuh-3+ No. scored sac non-sac % sac
tuk-3/Df No. scored sac
non-sac
% sac
D f sbd1"5/rucues D f sbd105/rucuca Df bxd'OO/TMi Df P2/T(2;3)ap"a Df PIO/TMf Df UbxlOQ/Xa
FMA3, y * / Y ;2-3 FMA3, y2/Y; e 3 FMA3, y"Y; 2-3 FMA3, y * / Y ;2-3 FMA3, y*/Y; 2-3 FMA3, y*/Y; 2-3
0 0 0 2 0 0
316 65 455 196 124 167
0.0 0.0 0.0 1.0 0.0 0.0
0 0 0 1 0 0
364 75 457 228 108 201
0.0 0.0 0.0 0.4 0.0 0.0
D f P9/Dp P5 tuh (UCF) Dp bxd'00-Df P I I 5 / T M l Df P i I S / T M i Df C4/Dp P5 Df bxd'l'/TMi
FMA3, y 2 / Y ;2-3 tuh-1s; D f PS/Dp P5 M 5 ; 2-3 M 5 ; 2-3 FMA3, y*/Y; 2-3 tuh-18; sbd tuh-3/TMi
1 0 0 0 1 1
634 747 699 153 261 243
0.2 0.0 0.0 0.0 0.4 0.4
45 84 121 58 112 102
30 42 135 53 38 26
60.0 66.7 47.3 52.5 74.7 79.7
Dp P I 1 5 / T M i D f P9/Dp P5 Df P9/Dp P5 Df P i f 5 / T M I Dp bxd'oO-Df P l l 5 / T M i
(tuh-is) Canton-S tuh(UCF) Canton-S iuh(UCF) Canton-S
0 0 0 0 0
182 521 342 650 333
0.0 0.0 0.0 0.0 0.0
0 9 U 0 3
122 270 155 201 289
0.0 3.2 0.0 0.0 1.0
iuh-3/tuh 3
:uh-3+/tuh-3+
Iv5; 2-3 Luh(UCF) Canton-S Oregon-R-C
M 5 ; 2-3 FMA3, y"Y; 2-3 Canton-S Oregon-R-C
2 378 0 0
909 427
334 791
0.6 32.8
0.0 0.0
P2, Df PIO, and D f UbxlOgdid not uncover tuh-3. For each cross involving deletions, internal comparisons were made between the balancer chromosomes with tuh-?+ / tuh-3 or (Dp P5) tuh-?+ t ~ h - 3 ~ l t u h - 3to Dfltuh-? males. No sactestes were found for Df sbd105,Df bxdlOO,Df PZO or for Df UbxlOg.The Df P2/ tuh-3 males had only 0.4% penetrance or one male affected while the internal control of tuh-3/T(2,?) apxumales had 1.0% penetrance. The tuh-? gene was uncovered by Df P9, Dp bxdlOo-Df PI15, Df C4 and Df bxdl" (Table 1 ) . The minimum penetrance of the trait was 47.3%, while maximum penetrance was 79.7%. Average penetrance was 61.7%. To show that deletions for the tuh-3+ region do not produce the sac-testis phenotypes, aneuploid males (Dfltuh-3 '.) were scored for the trait. Canton-S females carry tuh-lg, so that the sac-testis maternal effect substance is laid down in the egg cytoplasm; yet, only 0.5% of the males showed the phenotype (Table 1). The tuh-Zg gene is required for a significant expression of the sac-testis maternal effect since male Df P115/tuh-? did not express the trait when the mother was homozygous for tuh-Ih [tuh(UCF)1. Unexpectedly, 3.2% Df P9/ tuh-? males possessed sac-testes when the mother carried tuh-Ih [tuh(UCF)1.
LOCATION OF
tuh-3 IN D. melanogaster
103
To uncover tuh-3 (sac-testis gene), the distal-most effect of the deletion must at least include iab-8 (as mapped by LEWIS1978). Df Ubx*Og,Df P2 and Df PI0 do not uncover iab-8. Our results indicate that tuh-3 (sac-testis gene) is uncovered by deletions that extend distally beyond the Ubx1O9and include iab-8. On the salivary gland chromosome map, the tuh-3 (sac-testis) gene mapped to approximately 8934-5 (see Table 2 for a summary of these results). Dosage of tuh-3: When tuh-3 acts in the presence of the sac-testis maternal effect, it does so as a recessive with reduced penetrance. I n tuh-3/tuh-3 males, 32.3% showed sac-testes (Table 1). While testing for tuh-3 among the crossovers recovered between sbd2 and bx3 (KUHNand WOODS, in press), a gene enhancing both the tumorous-head and sac-testis maternal effects was discovered. Males sbdz tuh-3/tuh-3 showed an increase in penetrance of the sactestis trait to 46.7% ( n = 772). As expected, when tuh-3/Df males were studied, the penetrance increased again, ranging from a low of 47.2% to a high of 79.7% (Table 1) averaging 61.7% penetrance. Penetrance reached 100% in sbd" tuh-3/Df P9 flies ( n = 58). Expressivity was so extreme in males and females alike that no internal or external genitalia were found. DISCUSSION
TWOgeneral conclusions result from deletion studies of tuh-3. First, the tuh-3 gene cannot be localized utilizing the tuh effect because it is semidominant and has reduced penetrance (KUHN and WOODS1982). Second, tuh-3 maps to band 8934 or 5 on the salivary gland chromosome map when it acts with tuh-Ig. A crucial issue was to establish that tuh-3 causes both defects, depending on which allele of the tuh-I maternal gene, tuh-lh or tuh-lg, is present. An alternative to this hypothesis is that two genes (tuh-3) and (sac-3) might exist in the tumorous-head chromosome 3 so that the sac-3 effect is seen with tuh-lg and tuh-3 activity is seen with the tuh-lh. Both genes could have arisen simultaneously and be so tightly linked as to minimize crossing over between them. KUHN, WOODSand COOK (1981) analyzed a situation where spontaneous mutations to bx9 and iab-2 arose simultaneously in the tumorous-head chromosome 3. Both mutants map to 3-58.8. During the work of WOOLF(1968) and KUHN and WOODS(1982), a total of 171 crossover events in a 12-mapunit interval between cu and sr were analyzed. All recombinant strains found to possess tuh traits also showed sac-testis maternal effect activity. Even though both of these studies were of limited value in mapping tuh-3, they provided data supporting WOOLF'S(1968) contention that tuh-3 causes both the tumorous-head and sac-testis traits. We further searched for separation of effects among 21 crossovers between pbx and fl, a map distance of approximately one unit (unpublished data). Complete concordance was once again found; 15 showed both traits and six showed neither. Based upon all available data, we conclude that tuh-3 accounts for both traits; yet, the point is difficult to prove. If two genes are responsible, they must be tightly linked. Cloning this region should clarify the situation.
104
D. T. KUHN, D. F. WOODS A N D D. J.ANDREW
Lr'
z
h
5-
LOCATION OF
tuh-3 IN D. melunogaster
105
Now that the tuh-3 gene has been shown to be on the distal side of the BX-C at iab-8, or separated to the right, it is necessary to establish how the gene functions. The BX-C houses a series of genes that control segmentation in Drosophila. These genes have been instrumental in dipteran evolution from multi-legged ancestors (LEWIS1978). With the exception of pbx, the chromosomal order of the genes parallels the order in which they control the thoracic and abdominal segments (LEWIS1978). It is premature to state unequivocally that tuh-3 resides within the BX-C. However, in adult flies, the absence of genitalia is the criterion for the presence of iub-8. So, it is quite possible that tuh-3 ("3) is a weak allele at this locus and that enhanced expression in tuh-19; Df P9/sbd tuh-3 flies results in an extreme iab-8 phenotype where no genitalia are present. The deletion mapping data are certainly compatible with this hypothesis. If it follows the pattern for the BX-C, the tuh-3 effect should involve posterior structures. The most extreme expression of the genital disc defect vividly demonstrates the effect on the modified posterior abdominal segments that have fused to form the genital disc. In the presence of tuh-19; Df P9/sbdetuh-3, flies possess no internal or external structures derived from the genital disc. The tumorous-head phenotype results from the combined effects of tuh-3 with the tumorous-head maternal effect gene tuh-lh. On the surface, the presence of head abnormalities ascribed to the action of a posterior regulating gene seems contradictory. However, the homoeotic alterations found in the head are primarily to posterior structures. In the female tumorous-head eye, we found 6th, 7th and 8th abdominal tergites, while the 6th tergite was found in the 1979). Less frequently, we can identify male (KUHN, ZUST and ILLMENSEE well-formed female and male genital structures such as female 8th tergite, vulva, vaginal teeth and anal plate. I n the male, we observe clasper teeth, anal plate, lateral plate and other genital structures. Homoeotic genital structures demonstrate a sexual dimorphism, with some female genital structures appearing in different parts of the head from where male genitalia appear (unpublished data). Both effects of tuh-3 involve posterior structures. We suggest that the regulation of tuh-3 is similar to that envisioned for the bithorax complex genes by LEWIS (1978). The tuh-3+ gene is active in the posterior end of the embryo, where it suppresses development of more anterior segments. The wild-type product is vital, so that complete absence of a tuh-3+ gene product leads to lethality, as was suggested for ssa (BOWNES,BOURNIASVARDIABASIS and SPARE1979). The tuh-3 product is probably normal; however, its regulation is abnormal. Turning attention to gene action of tuh-3 under the influence of tuh-l", the gene function is described as recessive with reduced penetrance. Recessive mutations may be hypomorphs or amorphs (SHEARN1978). An amorph produces no functional gene product. A hypomorph has less than the normal level of activity. Under the influence of tuh-lg, tuh-3 acts as though there is a reduction in amount of product. Penetrance increases as gene activity decreases (i.e., tuh-3/tuh-3 (32.3% penetrance) < sbd tuh-3/tuh-3 (46.7%) < tuh-3/Df (61.7%) < sbd tuh-3lDf (100%).
106
D. T.
KUHN, D. F. WOODS A N D D. J . A N D R E W
One homoeotic effect of tuh not yet addressed is the transformation of antennal tissue to leg in flies showing the tumorous-head maternal effect. Presence of leg i n antennal disc derivatives does not lend support to the view that tuh-3 acts specifically on posterior structures. STRUB(1980) suggested that, at least for the antenna to leg transformation seen in A r ~ t p ~cell ” ~death , in the antennal disc exposes “homoeosis-competent” cells to different positional information, which results in transdetermination to distal leg. A similar case was made by DENELL(1978) for mutant alleles at the Polycomb locus. In our studies of tuh imaginal discs, wide-spread cell death was observed. Cell death i n the tuh eyeantennal disc has been seen by RUSSELL(personal communication) and by BOURNIAS-VARDIABASIS and BOWNES(1980). Antennal transformation to leg in tuh may not be a direct result of primary gene action, but rather from seconda r y effects of tuh-3 leading to cell death. For their helpful comments on the manuscript. we thank J. N. AHEARN,H. NICIILA,and R. NOTHIGER.Special thanks are extended to E. B. LEWISfor his suggestions and for allowing us to use his series of deletions and to C. M. WOOLFfor many valuable discussions. Criticisms and suggestions by the anonymous reviewers have significantly improved this paper. F. C. WALKER provided excellent technical assistance. The work was supported by National Science Foundation Grant PCM77-13966 and Public Health Service Grant R01 AG-01846. LITERATURE CITED
B ~ ~ R N I A ~ - V A R D IN. AB and A ~M. I ~BOWNES, , 1978 Genetic analysis of the tumorous-head mutation in D . melanogaster. Drosophila Inform. S e n . 53: 190. -, 1980 Cell death in the tumorous-head mutant of D. melanogaster. Drosophila Inform. Serv. 55: 17. BOWNES, M., N. BOURNIAS-VARDIABASIS and W. J. SPARE,1979 Genetic analysis of the spineless-aristapedia homoeotic mutants of Drosophila melanogaster. Molec. Gen. Genet. 174: 67-74. DENELL,R. E., 1978 Homoeosis in Drosophila. 11. A genetic analysis of Polycomb. Genetics 90: 277-289. GARCIA-BELLIDO. A., 1977 Homoeotic and atavic mutations in insects. Am. Zoologist 17: 613-629. GARDNER. E. J., 1959 Genetic mechanism of maternal effect for tumorous-head in Drosophila melanogaster. Genetics 44: 471481.
E. J. and C. M. WOOLF,1949 Maternal effect involved in the inheritance of abGARDNER, normal growths in the head region of Drosophila melanogaster. Genetics 34: 573-585. T. C.. R. LEWISand B. WAKIMOTO, 1980 Cytogenetic analysis of chromosome 3 KAUFMAN, in Drosophila mehogaster: The homoeotic gene complex in polytene chromosome interval 84A-B. Genetics 94: 115-133. KUHN,D. T., 1970 The interaction between the Payne inversion and genetic background in 1974 the tumorous-head strain of Drosophila melanogaster. Evolution 24: 181-187. -, Relationships between eclosion. sex ratio. karyotype. penetrance, and larval competition in a tumorous-head strain of Drosophila melanogaster. Drosophila Inform. Serv. 51: 102-1 04. KUHN, D. T. and S. F. DORGAN, 1975 Homoeotic effect of the tumorous-head mutant and differential effect of an enhancer gene in the tumorous-head strain of Drosophila melanogaster. Can. J. Genet. Cytol. 17: 423432.
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KUHN,D. T. and D. F. WOODS,1982 Localization of tuh-3 in D. melanogaster. Drosophila Inform. Serv. (In press.) KUHN,D. T., D. F. WOODS and J. L. COOK,1981 Analysis of a new homoeotic mutation (iab-2) within the bithorax complex in Drosophila melanoguster. Molec. Gen. Genet. 181: 82-86. KUHN, D. T., B. ZUST and K. ILLMENSEE, 1979 Autonomous differentiation of the tumoroushead phenotype in Drosophila melanogaster. Molec. Gen. Genet. 160: 117-124. 1964 LEWIS,E. B., 1963 Genes and developmental pathways. Am. Zoologist 3: 33-56. -, Genetic control and regulation of developmental pathways. pp. 231-252. In: Role of Chromosomes in Development. Edited by M. LOCKE.Academic Press, New York. -, 1978 A gene complex controlling segmentation in Drosophila. Nature 276: 565-570. 1980 New mutants report in D. melanogastzr. Drosophila Inform. Serv. 55: 207. $-
LINDSLEY, D. L. and E. H. GRELL,1968 Genetic variations of Drosophila melanogaster. Carnegie Inst. Wash. Publ. No. 627. NEWBY,W. W., 1949 Abnormal growths on the head of Drosophila melanogaster. J. Morphology 85: 177-196.
J. H., P. J. BRYANT and G. SCHUBIGER, 1972 The homoeotic effect of "tumorPOSTLETHWAIT, ous-head" in Drosophila melanogaster. Develop. Biology 29: 337-342. PYATI, J., 1976 Cytological localization of the maternal effect gene, tuh-l in Drosophila melanogaster. Mol. Gen. Genet. 146: 189-190. SHEARN, A., 1978 Mutational dissection of imaginal disc development, pp. 443-510. In: The Genetics and Biology of Drosophila, Vol. 2c. Edited by M. ASHBURNER and E. NOVITSKI. Academic Press, New York and London. STRAUB,S., 1980 Heteromorphic regeneration in the developing imaginal primordia of Drosophila. pp. 311-324. In: Cell Lineage and Stem Cell Determination. Edited by N. LE DOUARIN. Elsevier/North Holland Biomedical Press, Amsterdam. WOOLF,C. M., 1965 Genetic divergence among tumorous-head strains of Drosophila melanogaster. Genetics 52: 809-817. -, 1966 Maternal effect influencing male genital disc development in Drosophila melanogaster. Genetics 53 : 295-302. -, 1968 Male genital disc defect in Drosophila melanogaster. Genetics 60: 111-121. WOOLF,C. M. and B. B. KNOWLES, 1964 Interchromosomal control of karyotype fitness in the tumorous-head strain of Drosophila melanogaster. Genetics 49: 165-173. WOOLF,C. M. and M. 0. LOTT,1965 Relationship between penetrance and karyotype in the tumorous-head strain of Drosophila melanogaster. Am. Naturalist 99: 511-513. WOOLF,C. M. and M. P. PASSAGE, 1980 Genetic variability of the tumorous-head maternal effect in Drosophila melanogaster. Molec. Gen. Genet. 178: 423-427. WOOLF,C. M. and L. J. PHELPS, 1960 Chromosomal polymorphism in the tumorous-head strain of Drosophila melanogaster. Science 132 : 1256-1257. Corresponding editor: T. C. KAUFMAN
