How an organism determines which of two alternative pathways of sexual differentiation to follow is a fundamental problem in development. In C. elegans, a free-living soil nematode, the ratio of X chromosomes to sets of autosomes determines whether the organism develops into a self-fertilizing hermaphrodite (2A:2X) or a male (2A:1X). In addition, a set of autosomal genes responsive to the chromosome balance has been identified as essential for either hermaphrodite development or male development. 1. One of our aims is to determine how C. elegans assesses the ratio of X chromosomes to autosomes and how this measurement affects the expression of sex-determining genes and dosage-compensating genes downstream in the pathway. One approach is a genetical one, isolating male and hermaphrodite lethal mutations and suppressors of genes known to be involved in dosage compensation. A second approach is to perform a descriptive analysis at the cellular level, of intersexual animals, induced either by mutation or by altering X dosage. This description will provide a broader framework in which to think about the consequences of altering the correct assessment of the X:A ratio. Because sexual differentiation is determined by the chromosomal composition, it is often necessary to impose a further mechanism to insure that expression of genes on sex chromosomes is kept equal in the different sexes. 2. another aim is to gain an understanding of the mechanism of dosage compensation. Our approach is to analyze genetically and biochemically loci known to affect the expression of X-linked genes and to identify new loci involved in this process. The biochemical analysis involves assaying X-linked gene expression in animals with mutations suspected to alter dosage compensation in order to determine if, in fact, they do. In addition, the analysis involves the molecular cloning of loci involved in dosage compensation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM030702-08
Application #
3278516
Study Section
Genetics Study Section (GEN)
Project Start
1982-09-01
Project End
1990-05-31
Budget Start
1989-09-01
Budget End
1990-05-31
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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Farboud, Behnom; Meyer, Barbara J (2015) Dramatic enhancement of genome editing by CRISPR/Cas9 through improved guide RNA design. Genetics 199:959-71
Crane, Emily; Bian, Qian; McCord, Rachel Patton et al. (2015) Condensin-driven remodelling of X chromosome topology during dosage compensation. Nature 523:240-4
Maxwell, Colin S; Kruesi, William S; Core, Leighton J et al. (2014) Pol II docking and pausing at growth and stress genes in C. elegans. Cell Rep 6:455-66
Farboud, Behnom; Nix, Paola; Jow, Margaret M et al. (2013) Molecular antagonism between X-chromosome and autosome signals determines nematode sex. Genes Dev 27:1159-78

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