Roles of SPD-3 during C. elegans meiosis
Author(s)
Labrador Gonzalez, Leticia
Type
Thesis
Abstract
Correct chromosome segregation during meiosis requires that the paternal and
maternal copies of each chromosome, known as homologues, recognise and pair with
one another before they can undergo meiotic recombination. Defects in this process
lead to sterility and the formation of aneuploid gametes, which is the leading cause of
birth defects in humans. In this study the process of homologue pairing during meiosis
has been investigated in C. elegans, an organism especially well suited for meiotic
studies. During a genetic screen for meiotic mutants, several mutants with defects in
meiotic chromosome segregation were isolated. One of these mutants, me85, was
identified as a new allele of the spd-3 gene, which had previously been shown to be
required for mitotic divisions in the early embryo. spd-3(me85) mutants display
defects in homologue pairing similar to those observed in mutants lacking SUN-1 or
ZYG-12, two proteins that form a bridge across the nuclear envelope (NE). This
bridge transmits cytoskeletal forces generated outside the nucleus to meiotic
chromosomes inside the nucleus, thereby facilitating chromosome clustering, a
process that is though to facilitate homology search. The localisation of SUN-1 and
ZYG-12 to the NE is not affected in spd-3(me85) mutants and chromosomes remain
tethered to the NE. However, live imaging experiments in spd-3(me85) mutants
demonstrate that the movement of chromosomes through the NE is severely impaired,
which results in lack of chromosome clustering. Knocking down the activity of the
dynein-dynactin complex by RNAi resulted in a phenocopy of the chromosome
clustering defects observed in spd-3(me85) mutants, although dynein localisation is
not affected in spd-3(me85) mutants. Interestingly, the SPD-3 protein localizes
outside the nucleus in the germline. These observations suggest that SPD-3 affects the
earliest steps of homologue pairing by regulating the cytoskeletal forces outside the
nucleus.
maternal copies of each chromosome, known as homologues, recognise and pair with
one another before they can undergo meiotic recombination. Defects in this process
lead to sterility and the formation of aneuploid gametes, which is the leading cause of
birth defects in humans. In this study the process of homologue pairing during meiosis
has been investigated in C. elegans, an organism especially well suited for meiotic
studies. During a genetic screen for meiotic mutants, several mutants with defects in
meiotic chromosome segregation were isolated. One of these mutants, me85, was
identified as a new allele of the spd-3 gene, which had previously been shown to be
required for mitotic divisions in the early embryo. spd-3(me85) mutants display
defects in homologue pairing similar to those observed in mutants lacking SUN-1 or
ZYG-12, two proteins that form a bridge across the nuclear envelope (NE). This
bridge transmits cytoskeletal forces generated outside the nucleus to meiotic
chromosomes inside the nucleus, thereby facilitating chromosome clustering, a
process that is though to facilitate homology search. The localisation of SUN-1 and
ZYG-12 to the NE is not affected in spd-3(me85) mutants and chromosomes remain
tethered to the NE. However, live imaging experiments in spd-3(me85) mutants
demonstrate that the movement of chromosomes through the NE is severely impaired,
which results in lack of chromosome clustering. Knocking down the activity of the
dynein-dynactin complex by RNAi resulted in a phenocopy of the chromosome
clustering defects observed in spd-3(me85) mutants, although dynein localisation is
not affected in spd-3(me85) mutants. Interestingly, the SPD-3 protein localizes
outside the nucleus in the germline. These observations suggest that SPD-3 affects the
earliest steps of homologue pairing by regulating the cytoskeletal forces outside the
nucleus.
Date Issued
2012
Date Awarded
2012-03
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Martinez-Perez, Enrique
Publisher Department
MRC Clinical Sciences Centre
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)