Abstract:How living systems break symmetry in an organized manner is a fundamental question in biology. In wild-type Caenorhabditis elegans zygotes, symmetry breaking during anterior-posterior axis specification is guided by centrosomes, resulting in anterior-directed cortical flows and a single posterior PAR-2 domain. We uncover that C. elegans zygotes depleted of the Aurora A kinase AIR-1 or lacking centrosomes entirely usually establish two posterior PAR-2 domains, one at each pole. We demonstrate that AIR-1 prevent… Show more
“…A similar distribution of phenotypes was observed in embryos from worms subject to partial plk-1(RNAi) in which ovulation still occurred ( Figure 5 B) and air-1(RNAi) worms expressing GFP::PAR-2 from the endogenous locus ( Table S1 ). Consistent with our observations, previous work has described a similar mix of phenotypes [ 30 , 33 , 38 , 39 , 40 ]. Figure 5 AIR-1 or PLK-1 Loss Induces Aberrant Polarization by Non-Canonical Cues (A) Examples of normal/paternal (left), reversed/maternal (middle) and bipolar (right) embryos shown (NWG26).…”
Section: Resultssupporting
confidence: 93%
“…The PAR network is responsive to various cues, reportedly including the meiotic spindle, microtubules, and membrane curvature (here and [ 4 . 19 , 38 , 39 ]). As we show, even spontaneously maturing unfertilized oocytes are able to polarize.…”
Summary
How do cells polarize at the correct time and in response to the correct cues? In the
C. elegans
zygote, the timing and geometry of polarization rely on a single dominant cue—the sperm centrosome—that matures at the end of meiosis and specifies the nascent posterior. Polarization requires that the conserved PAR proteins, which specify polarity in the zygote, be poised to respond to the centrosome. Yet, how and when PAR proteins achieve this unpolarized, but responsive, state is unknown. We show that oocyte maturation initiates a fertilization-independent PAR activation program. PAR proteins are initially not competent to polarize but gradually acquire this ability following oocyte maturation. Surprisingly, this program allows symmetry breaking even in unfertilized oocytes lacking centrosomes. Thus, if PAR proteins can respond to multiple polarizing cues, how is specificity for the centrosome achieved? Specificity is enforced by Polo-like and Aurora kinases (PLK-1 and AIR-1 in
C. elegans
), which impose a delay in the activation of the PAR network so that it coincides with maturation of the centrosome cue. This delay suppresses polarization by non-centrosomal cues, which can otherwise trigger premature polarization and multiple or reversed polarity domains. Taken together, these findings identify a regulatory program that enforces proper polarization by synchronizing PAR network activation with cell cycle progression, thereby ensuring that PAR proteins respond specifically to the correct cue. Temporal control of polarity network activity is likely to be a common strategy to ensure robust, dynamic, and specific polarization in response to developmentally deployed cues.
“…A similar distribution of phenotypes was observed in embryos from worms subject to partial plk-1(RNAi) in which ovulation still occurred ( Figure 5 B) and air-1(RNAi) worms expressing GFP::PAR-2 from the endogenous locus ( Table S1 ). Consistent with our observations, previous work has described a similar mix of phenotypes [ 30 , 33 , 38 , 39 , 40 ]. Figure 5 AIR-1 or PLK-1 Loss Induces Aberrant Polarization by Non-Canonical Cues (A) Examples of normal/paternal (left), reversed/maternal (middle) and bipolar (right) embryos shown (NWG26).…”
Section: Resultssupporting
confidence: 93%
“…The PAR network is responsive to various cues, reportedly including the meiotic spindle, microtubules, and membrane curvature (here and [ 4 . 19 , 38 , 39 ]). As we show, even spontaneously maturing unfertilized oocytes are able to polarize.…”
Summary
How do cells polarize at the correct time and in response to the correct cues? In the
C. elegans
zygote, the timing and geometry of polarization rely on a single dominant cue—the sperm centrosome—that matures at the end of meiosis and specifies the nascent posterior. Polarization requires that the conserved PAR proteins, which specify polarity in the zygote, be poised to respond to the centrosome. Yet, how and when PAR proteins achieve this unpolarized, but responsive, state is unknown. We show that oocyte maturation initiates a fertilization-independent PAR activation program. PAR proteins are initially not competent to polarize but gradually acquire this ability following oocyte maturation. Surprisingly, this program allows symmetry breaking even in unfertilized oocytes lacking centrosomes. Thus, if PAR proteins can respond to multiple polarizing cues, how is specificity for the centrosome achieved? Specificity is enforced by Polo-like and Aurora kinases (PLK-1 and AIR-1 in
C. elegans
), which impose a delay in the activation of the PAR network so that it coincides with maturation of the centrosome cue. This delay suppresses polarization by non-centrosomal cues, which can otherwise trigger premature polarization and multiple or reversed polarity domains. Taken together, these findings identify a regulatory program that enforces proper polarization by synchronizing PAR network activation with cell cycle progression, thereby ensuring that PAR proteins respond specifically to the correct cue. Temporal control of polarity network activity is likely to be a common strategy to ensure robust, dynamic, and specific polarization in response to developmentally deployed cues.
“…Especially, the segregation of PAR proteins is induced by the intrinsic cue from centrosomes in C. elegans zygotes (Klinkert et al, 2019;Reich et al, 2019;Zhao et al, 2019). In contrast, our findings highlight that the self-organizing property of antagonizing PAR proteins serves as an active cue that instructs the intrinsic cell-division program in two-cell stage embryos.…”
Section: Discussionmentioning
confidence: 67%
“…In contrast, our findings highlight that the self-organizing property of antagonizing PAR proteins serves as an active cue that instructs the intrinsic cell-division program in two-cell stage embryos. Recent studies observed delayed polarization of PAR proteins in zygotes depleted of a centrosome-mediated cue, Aurora-A (Klinkert et al, 2019;Reich et al, 2019;Zhao et al, 2019), suggesting the centrosome-independent self-organizing property of PAR proteins. We propose that unequal inheritance of the self-organizing property of PAR proteins plays a critical role in the binary specification of PAR patterning in two-cell stage embryos.…”
Coordination between cell differentiation and proliferation during development requires the balance between asymmetric and symmetric modes of cell division. However, the cellular intrinsic cue underlying the binary choice between these two division modes remains elusive. Here we show evidence in Caenorhabditis elegans that the invariable lineage of the division modes is programmed by the balance between antagonizing complexes of partitioning-defective (PAR) proteins. By uncoupling unequal inheritance of PAR proteins from that of fate determinants during zygote division, we demonstrated that changes in the balance between PAR-2 and PAR-6 are sufficient to re-program the division modes from symmetric to asymmetric and vice versa in two-cell stage embryos. The division mode adopted occurs independently of asymmetry in cytoplasmic fate determinants, cell-size asymmetry, and cell-cycle asynchrony between the sister cells. We propose that the balance between antagonizing PAR proteins represents an intrinsic self-organizing cue for binary specification of the division modes during development.
“…SB occurs approximately 30 minutes after fertilisation when local relaxation of contractility of the cell cortex in the vicinity of SPCC occurs, which is the earliest sign of the establishment of the AP polarity 9,10 . At this time, Aurora A kinase (AIR-1) is known to relocate from the cytoplasm to the centrosomes [11][12][13] . The local relaxation triggers unidirectional advection of the cortical actomyosin that brings the anterior PAR proteins to the future anterior cortex, and simultaneously the posterior PAR proteins are allowed to localise to the future posterior cortex 1,14 .…”
Cell polarisation is required to define body axes during development. The position of spatial cues for polarisation is critical to direct the body axes. In Caenorhabditis elegans zygotes, the sperm-derived pronucleus/centrosome complex (SPCC) serves as the spatial cue to specify the anterior-posterior axis.Approximately 30 minutes after fertilisation, the contractility of the cell cortex is relaxed near the SPCC, which is the earliest sign of polarisation and called symmetry breaking (SB). It is unclear how the position of SPCC at SB is determined after fertilisation. Here, we show that SPCC drifts dynamically through the cell-wide flow of the cytoplasm, called meiotic cytoplasmic streaming.This flow occasionally brings SPCC to the opposite side of the sperm entry site before SB. Our results demonstrate that cytoplasmic flow determines stochastically the position of the spatial cue of the body axis, even in an organism like C. elegans for which development is stereotyped.
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