scholarly journals The Mutation masculinizer (man) Defines a Sex-Determining Gene With Maternal and Zygotic Functions in Musca domestica L.

Genetics ◽  
1997 ◽  
Vol 145 (1) ◽  
pp. 173-183 ◽  
Author(s):  
R Schmidt ◽  
M Hediger ◽  
R Nöthiger ◽  
A Dübendorfer
Keyword(s):  
Musca Domestica ◽  
Maternal Effect ◽  
Dominant Factor ◽  
Loss Of Function ◽  
New Mutation ◽  
Yolk Proteins ◽  
Hypomorphic Allele ◽  
Internal Structures ◽  
Primary Signal ◽  
Pole Cells

In Musca domestica, the primary signal for sex determination is the dominant factor M, which is assumed to regulate a postulated female-determining gene F. Presence of M prevents expression of F so that male development ensues. In the absence of M, F can become active, which dictates the female pathway. The existence of F is inferred from FD, a dominant factor that is epistatic to M. We describe a new mutation masculinizer, which has all the properties expected for a null or strongly hypomorphic allele of F: (1) it maps to the same chromosomal location as FD, (2) homozygous man/man animals develop as males, (3) homozygous man/man clones generated in man/+ female larvae differentiate male structures, (4) man has a sex-determining maternal effect. About a third of the morphological males synthesize yolk proteins, which indicates that they are intersexual in internal structures. The maternal effect of man is complete in offspring that derive from homozygous man/man pole cells transplanted into female hosts. In this case, all man/+ progeny become fertile males that do not produce yolk proteins. A sex-determining maternal effect has previously been demonstrated for FD. Like F, maternal man  + is needed for zygotic man  + to become active, providing further evidence that man is a loss-of-function allele of F.

Genetic control of sex determination in the germ line and soma of the housefly, Musca domestica

Development ◽  
1994 ◽  
Vol 120 (9) ◽  
pp. 2531-2538 ◽  
Author(s):  
D. Hilfiker-Kleiner ◽  
A. Dubendorfer ◽  
A. Hilfiker ◽  
R. Nothiger
Keyword(s):  
Sex Determination ◽  
Musca Domestica ◽  
Germ Cells ◽  
Maternal Effect ◽  
Germ Line ◽  
M Cells ◽  
Female Genotype ◽  
Female Germ Line ◽  
Pole Cells

In Musca domestica, sex in the soma is cell autonomously determined by the male-determiner M, or by the female-determiner FD. Transplanted pole cells (precursors of the germ line) show that sex determination of germ cells is non-autonomous genotypically male pole cells form functional eggs in female hosts, and genotypically female pole cells form functional sperm in male hosts. When M/+ cells undergo oogenesis, a male-determining maternal effect predetermines offspring without M, i.e. of female genotype, to develop as fertile males. FD is epistatic to M in the female germ line, as it is in the soma, overruling the masculinizing effect of M. The results suggest that maternal F product is needed for activation of the zygotic F gene.

scholarly journals The Y-Chromosomal and Autosomal Male-Determining M Factors of Musca domestica Are Equivalent

Genetics ◽  
1997 ◽  
Vol 147 (1) ◽  
pp. 271-280
Author(s):  
R Schmidt ◽  
M Hediger ◽  
S Roth ◽  
R Nöthiger ◽  
A Dubendorfer
Keyword(s):  
Musca Domestica ◽  
Germ Line ◽  
Dominant Factor ◽  
Sensitive Period ◽  
Temperature Sensitive ◽  
Female Development ◽  
Dominant Female ◽  
Female Germ Line ◽  
Pole Cells ◽  
Determining Factor

Abstract In Musca domestica, male sex is determined by a dominant factor, M, located either on the Y, the X or on an autosome. M prevents the activity of the female-determining gene F. In the absence of M, F becomes active and dictates female development. The various M factors may represent translocated copies of an ancestral Y-chromosomal M. Double mutants and germ line chimeras show that MY, MI, MII, MIII and MV perform equivalent functions. When brought into the female germ line, they predetermine male development of the offspring. This maternal effect is overruled by the dominant female-determining factor FD. MI and MII are weak M factors, as demonstrated by the presence of yolk proteins in MI/+ males and by the occurrence of some intersexes among the offspring that developed from transplanted MI/+ and MII/+ pole cells. The arrhenogenic mutation Ag has its focus in the female germ line and its temperature-sensitive period during oogenesis. We propose that MI and Ag represent allelic M factors that are affected in their expression. Analysis of mosaic gonads showed that in M. domsticu the sex of the germ line is determined by inductive signals from the surrounding soma. We present a model to account for the observed phenomena.

Study of the development of the internal organs of the double malformations of Chironomus dorsalis by fixed and sectioned materials

Development ◽  
1970 ◽  
Vol 24 (2) ◽  
pp. 287-303
Author(s):  
Hideo Yajima
Keyword(s):  
Ventral Side ◽  
Dorsal Side ◽  
Second Step ◽  
Convex Side ◽  
Internal Organs ◽  
Flat Side ◽  
Internal Structures ◽  
Pole Cells ◽  
The One ◽  
Thoracic And Abdominal

The development of the internal structures was investigated by fixed sections of the ‘double cephalon’ and ‘double abdomen’ of Chironomus dorsalis. The cell proliferation that gives rise to ‘germ Anlage’ or embryonic rudiment begins, in the double cephalon, along the entire convex (ventral) side of the egg and, in the double abdomen, at both ends of the flat (dorsal) side. As a result, a single fused Anlage of the double cephalon appears along the entire convex side of the egg and two germ Anlagen of the double abdomen appear at both ends of the flat side. During the formation of the germ band, both the posteriormost part of the double cephalon which lies at the middle of the convex side of the egg and the anteriormost part of the double abdomen which is located at the middle of the convex side, fail to differentiate and later degenerate. In each of the duplicated heads of double cephalon, cephalic segments anterior to the first maxillary segment are formed, but the thoracic and abdominal segments are entirely missing. In each half of the double abdomen, eight abdominal segments posterior to the second abdominal segment are produced and the cephalic and thoracic segments are omitted altogether. The two pairs of mid-gut rudiment from both halves of the double cephalon are temporarily united but they break apart by the end of the blastokinesis. When the two pairs of mid-gut rudiment from both halves of the double abdomen meet, they remain fused with each other, being surrounded by the visceral mesodermal cells in the normal way, and develop into the mid-gut epithelium. In the double malformations, the pole cells are contained in only one member of the duplicated structures. The pole cells of the double cephalon develop into the tetra-nucleate state (Hasper's second step), but they fail to fuse to form tte gonad. In the double abdomen, the gonad develops in the one abdomen containing the pole colls and no replacement occurs in the sister abdomen without the pole cells. The embryonic envelopes of the double cephalon do no' retract into the interior of the embryo, while they do in the normal way in the double abdomen. The double cephalon can never hatch but the double abdon en can emerge.

Dominant maternal-effect mutations causing embryonic lethality in Caenorhabditis elegans.

Genetics ◽  
1990 ◽  
Vol 125 (2) ◽  
pp. 351-369 ◽  
Author(s):  
P E Mains ◽  
I A Sulston ◽  
W B Wood
Keyword(s):  
Caenorhabditis Elegans ◽  
Maternal Effect ◽  
Gene Dosage ◽  
Recessive Mutation ◽  
Dominant Male ◽  
Temperature Sensitive ◽  
Male Mating ◽  
Loss Of Function ◽  
Dominant Mutant ◽  
Embryonic Viability

Abstract We undertook screens for dominant, temperature-sensitive, maternal-effect embryonic-lethal mutations of Caenorhabditis elegans as a way to identify certain classes of genes with early embryonic functions, in particular those that are members of multigene families and those that are required in two copies for normal development. The screens have identified eight mutations, representing six loci. Mutations at three of the loci result in only maternal effects on embryonic viability. Mutations at the remaining three loci cause additional nonmaternal (zygotic) effects, including recessive lethality or sterility and dominant male mating defects. Mutations at five of the loci cause visible pregastrulation defects. Three mutations appear to be allelic with a recessive mutation of let-354. Gene dosage experiments indicate that one mutation may be a loss-of-function allele at a haploin sufficient locus. The other mutations appear to result in gain-of-function "poison" gene products. Most of these become less deleterious as the relative dosage of the corresponding wild-type allele is increased; we show that relative self-progeny viabilities for the relevant hermaphrodite genotypes are generally M/+/+ greater than M/+ greater than M/M/+ greater than M/Df greater than M/M, where M represents the dominant mutant allele.

scholarly journals A hypomorphic allele of SLC35D1 results in Schneckenbecken-like dysplasia

2019 ◽  
Vol 28 (21) ◽  
pp. 3543-3551
Author(s):  
Carsten Rautengarten ◽  
Oliver W Quarrell ◽  
Karen Stals ◽  
Richard C Caswell ◽  
Elisa De Franco ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Missense Variant ◽  
Sugar Transporter ◽  
Loss Of Function ◽  
Transport Activity ◽  
Nucleotide Sugar ◽  
Gene Encoding ◽  
Hypomorphic Allele ◽  
Nucleotide Sugar Transporter

Abstract We report the case of a consanguineous couple who lost four pregnancies associated with skeletal dysplasia. Radiological examination of one fetus was inconclusive. Parental exome sequencing showed that both parents were heterozygous for a novel missense variant, p.(Pro133Leu), in the SLC35D1 gene encoding a nucleotide sugar transporter. The affected fetus was homozygous for the variant. The radiological features were reviewed, and being similar, but atypical, the phenotype was classified as a ‘Schneckenbecken-like dysplasia.’ The effect of the missense change was assessed using protein modelling techniques and indicated alterations in the mouth of the solute channel. A detailed biochemical investigation of SLC35D1 transport function and that of the missense variant p.(Pro133Leu) revealed that SLC35D1 acts as a general UDP-sugar transporter and that the p.(Pro133Leu) mutation resulted in a significant decrease in transport activity. The reduced transport activity observed for p.(Pro133Leu) was contrasted with in vitro activity for SLC35D1 p.(Thr65Pro), the loss-of-function mutation was associated with Schneckenbecken dysplasia. The functional classification of SLC35D1 as a general nucleotide sugar transporter of the endoplasmic reticulum suggests an expanded role for this transporter beyond chondroitin sulfate biosynthesis to a variety of important glycosylation reactions occurring in the endoplasmic reticulum.

scholarly journals The phenotypic variations of multi-locus imprinting disturbances associated with maternal-effect variants of NLRP5 range from overt imprinting disorder to apparently healthy phenotype

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Angela Sparago ◽  
Ankit Verma ◽  
Maria Grazia Patricelli ◽  
Laura Pignata ◽  
Silvia Russo ◽  
...  
Keyword(s):  
Maternal Effect ◽  
Multiple Pregnancy ◽  
Principal Component ◽  
Loss Of Function ◽  
Imprinting Disorders ◽  
Imprinting Disorder ◽  
Whole Exome ◽  
Genome Analyses ◽  
Methylation Patterns ◽  
And Control

Abstract Background A subset of individuals affected by imprinting disorders displays multi-locus imprinting disturbances (MLID). MLID has been associated with maternal-effect variants that alter the maintenance of methylation at germline-derived differentially methylated regions (gDMRs) in early embryogenesis. Pedigrees of individuals with MLID also include siblings with healthy phenotype. However, it is unknown if these healthy individuals have MLID themselves or if their methylation patterns differ from those associated with imprinting disorders, and in general, if MLID affects the clinical phenotype. Methods We have investigated gDMR methylation by locus-specific and whole-genome analyses in a family with multiple pregnancy losses, a child with Beckwith-Wiedemann syndrome (BWS) and a further child with no clinical diagnosis of imprinting disorder or other pathologies. Results We detected MLID with different methylation profiles in the BWS-affected and healthy siblings. Whole-exome sequencing demonstrated the presence of novel loss-of-function variants of NLRP5 in compound heterozygosity in the mother. The methylation profiles of the two siblings were compared with those of other cases with MLID and control groups by principal component analysis and unsupervised hierarchical clustering, but while their patterns were clearly separated from those of controls, we were unable to cluster those associated with specific clinical phenotypes among the MLID cases. Conclusion The identification of two novel maternal-effect variants of NLRP5 associated with poly-abortivity and MLID adds further evidence to the role of this gene in the maintenance of genomic imprinting in early embryos. Furthermore, our results demonstrate that within these pedigrees, MLID can also be present in the progeny with healthy phenotype, indicating that some sort of compensation occurs between altered imprinted loci in these individuals. The analysis of larger cohorts of patients with MLID is needed to formulate more accurate epigenotype-phenotype correlations.

scholarly journals PRDM15 loss of function links NOTCH and WNT/PCP signaling to patterning defects in holoprosencephaly

2020 ◽  
Vol 6 (2) ◽  
pp. eaax9852 ◽  
Author(s):  
Slim Mzoughi ◽  
Federico Di Tullio ◽  
Diana H. P. Low ◽  
Corina-Mihaela Motofeanu ◽  
Sheena L. M. Ong ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Transcriptional Activity ◽  
Embryonic Lethality ◽  
Loss Of Function ◽  
New Mutation ◽  
Brain Malformations ◽  
Pcp Signaling ◽  
Genetic Deletion ◽  
The Brain ◽  
Anterior Posterior

Holoprosencephaly (HPE) is a congenital forebrain defect often associated with embryonic lethality and lifelong disabilities. Currently, therapeutic and diagnostic options are limited by lack of knowledge of potential disease-causing mutations. We have identified a new mutation in the PRDM15 gene (C844Y) associated with a syndromic form of HPE in multiple families. We demonstrate that C844Y is a loss-of-function mutation impairing PRDM15 transcriptional activity. Genetic deletion of murine Prdm15 causes anterior/posterior (A/P) patterning defects and recapitulates the brain malformations observed in patients. Mechanistically, PRDM15 regulates the transcription of key effectors of the NOTCH and WNT/PCP pathways to preserve early midline structures in the developing embryo. Analysis of a large cohort of patients with HPE revealed potentially damaging mutations in several regulators of both pathways. Our findings uncover an unexpected link between NOTCH and WNT/PCP signaling and A/P patterning and set the stage for the identification of new HPE candidate genes.

The inheritance of diazinon resistance in an Australian strain of Musca domesticaL.

1963 ◽  
Vol 54 (3) ◽  
pp. 461-465 ◽  
Author(s):  
R. J. Hart
Keyword(s):  
Musca Domestica ◽  
Strong Evidence ◽  
Organic Phosphate ◽  
Dominant Factor ◽  
Frequency Data ◽  
House Flies ◽  
Response Information ◽  
Resistant Form ◽  
The Relationship

The genetics of diazinon resistance in an Australian strain of Musca domestica L. was investigated by means of two series of repeated back-crosses of the hybrid resistant form to the susceptible. Resistance was maintained through nine and eleven generations in the separate studies. The ratio of susceptible to resistant hybrid flies found in the progeny of each cross was approximately 1:1.In the second series, the frequency data were supported by dosage/response information on the relationship between dosage of insecticide and mortality. Together with the result of a previous study, the data furnish strong evidence that a fully dominant factor is responsible for the diazinon resistance in the Perth strain of house-flies resistant to organic phosphate insecticides.

scholarly journals Characterization of Suppressor of fused, a complete suppressor of the fused segment polarity gene of Drosophila melanogaster.

Genetics ◽  
1992 ◽  
Vol 132 (3) ◽  
pp. 725-736 ◽  
Author(s):  
T Préat
Keyword(s):  
Drosophila Melanogaster ◽  
Maternal Effect ◽  
Opposite Effect ◽  
Loss Of Function ◽  
Suppressor Of Fused ◽  
Segment Polarity ◽  
New Gene ◽  
Segment Polarity Gene ◽  
Polarity Gene

Abstract fused (fu) is a maternal effect segment polarity gene of Drosophila melanogaster. In addition, fu females have tumorous ovaries. Two ethyl methanesulfonate mutageneses were carried out in order to isolate suppressors of the fu phenotype. A new gene, Suppressor of fused (Su(fu)), was identified. It is located in the 87C8 region of the third chromosome. Su(fu) displays a maternal effect and is also expressed later in development. Although Su(fu)LP is a complete loss-of-function mutation, it is homozygous viable and has no phenotype by itself. Su(fu) fully suppresses the embryonic and adult phenotypes of fu mutants. Su(fu) mutations are semidominant and a Su(fu)+ duplication has an opposite effect, enhancing the fused phenotype. It is proposed therefore that the Su(fu)+ product is involved in the same developmental step as the Fu+ kinase. Thus, a new gene interacting with the segment polarity pathway was identified using an indirect approach.

scholarly journals Developmental analysis of two sex-determining genes, M and F, in the housefly, Musca domestica.

Genetics ◽  
1993 ◽  
Vol 134 (4) ◽  
pp. 1187-1194
Author(s):  
D Hilfiker-Kleiner ◽  
A Dübendorfer ◽  
A Hilfiker ◽  
R Nöthiger
Keyword(s):  
Musca Domestica ◽  
Larval Instar ◽  
Sex Reversal ◽  
Dominant Factor ◽  
Female Development ◽  
Male And Female ◽  
Female Genotype ◽  
Developmental Analysis ◽  
Blastoderm Stage ◽  
State Of Activity

Abstract In the housefly, Musca domestica, a single dominant factor, M, determines maleness. Animals hemi-or heterozygous for M are males, whereas those without M develop as females. In certain strains, however, both sexes are homozygous for M, and an epistatic dominant factor, FD, dictates female development. The requirement for these factors was analyzed by producing, with mitotic recombination, mosaic animals consisting of genetically male and female cells. Removal of FD from an M/M;FD/+ cell at any time of larval development, even in the last larval instar, resulted in sex-reversal, i.e., in the development of a male clone in an otherwise female fly. In contrast, when M was removed from M/+ cells, the resulting clones remained male despite their female genotype, even when the removal of M happened at embryonic stages. The occurrence of spontaneous gynandromorphs, however, shows that the loss of M in individual nuclei prior to blastoderm formation causes the affected cells to adopt the female pathway. These results are consistent with the hypothesis that M is the primary sex-determining signal which sets the state of activity of the key gene F at around the blastoderm stage. Parallels and differences to the sex-determining system of Drosophila are discussed.

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