Cullin-5 mutants reveal collective sensing of the nucleocytoplasmic ratio in Drosophila embryogenesis

Hayden, Luke; Chao, Anna T.; Deneke, Victoria E.; Vergassola, Massimo; Talia, Stefano Di

doi:10.1016/j.cub.2022.03.007

Cited by 10 publications

(11 citation statements)

References 57 publications

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“…Similar results were also found in the fruit fly D. melanogaster [36], further supporting the critical role of histones in sensing the N/C ratio, be it in early cleaving embryos like Xenopus or syncytial ones like Drosophila . Moreover, recent work suggested that the N/C ratio is not sensed globally at the level of the embryo in D. melanogaster , but rather locally at the level of a community of nuclei at the syncytial embryo cortex [37, 38]. This process is partly regulated by the activity of mitotic phosphatases including Protein phosphatase 1 (PP1) [27].…”

Section: Resultsmentioning

confidence: 99%

“…Localized activation of PP1, which spreads from the nuclei to the embryo cortex, activates cortical actomyosin in a spatially restricted manner. This leads to a localized increase in myosin II gradients, driving both cortical and cytoplasmic flows and ultimately ensuring efficient cellularization [24,27,37]. Given that several above-mentioned regulators have been identified in the genome of S. arctica [7,[39][40][41], we wondered whether similar pathways may be involved in sensing the N/C ratio.…”

Section: The N/c Ratio Is Locally Sensed At the Cortex During The Cel...mentioning

confidence: 99%

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The nuclear to cytoplasmic ratio drives cellularization in the close animal relativeSphaeroforma arctica

Olivetta

Dudin

2023

Preprint

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The ratio of nuclear content to cytoplasmic volume (N/C ratio) is a key regulator driving maternal-to-zygotic transition in most animal embryos. Altering this ratio often impacts zygotic genome activation and deregulates the timing and outcome of embryogenesis [1-3]. Despite being ubiquitous across animals, little is known about when the N/C ratio evolved to control multicellular development. Such capacity either originated with the emergence of animal multicellularity or was co-opted from mechanisms present in unicellular organisms [4]. An effective strategy to tackle this question is to investigate close relatives of animals exhibiting life cycles with transient multicellular stages [5]. Among these are ichthyosporeans, a lineage of protists undergoing coenocytic development followed by cellularization and cell release [6-8]. During cellularization, a transient multicellular stage resembling animal epithelia is generated offering a unique opportunity to examine whether the N/C ratio regulates multicellular development. Here, we use time-lapse microscopy to characterize how the N/C ratio affects the life cycle of the best-studied ichthyosporean model, Sphaeroforma arctica. We uncover that the last stages of cellularization coincide with a significant increase in the N/C ratio. Increasing the N/C ratio by reducing the coenocytic volume accelerates cellularization while decreasing the N/C ratio by lowering the nuclear content halts it. Moreover, centrifugation and pharmacological inhibitor experiments suggest that the N/C ratio is locally sensed at the cortex and relies on phosphatase activity. Altogether, our results show that the N/C ratio drives cellularization in S. arctica, suggesting that its capacity to control multicellular development predates animal emergence.

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Section: Resultsmentioning

confidence: 99%

Section: The N/c Ratio Is Locally Sensed At the Cortex During The Cel...mentioning

confidence: 99%

The nuclear to cytoplasmic ratio drives cellularization in the close animal relativeSphaeroforma arctica

Olivetta

Dudin

2023

Preprint

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“…Values are reported at the position of each nucleus. C) Experimental comparison of the Bicoid gradient at cell cycle 13 in wild-type and cullin-5 mutant embryos, where flows are strongly suppressed [29]. Datapoints were binned in each case, with the continuous line and error bars representing each bin’s average and standard error respectively.…”

Section: Resultsmentioning

confidence: 99%

“…As a result of this reduced nuclear movement, nuclear density across the embryos is highly non-uniform. In turn, this results in asynchronous cell cycles prior to the maternal-to-zygotic transition (MZT), which demonstrates the functional role of the flows [20, 28, 29].…”

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confidence: 99%

Two-fluid dynamics and micron-thin boundary layers shape cytoplasmic flows in earlyDrosophilaembryos

López

et al. 2023

Preprint

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Cytoplasmic flows are widely emerging as key functional players in development. In earlyDrosophila embryos, flows drive the spreading of nuclei across the embryo. Here, we combine hydrodynamic modeling with quantitative imaging to develop a two-fluid model that features an active actomyosin gel and a passive viscous cytosol. Gel contractility is controlled by the cell cycle oscillator, the two fluids being coupled by friction. In addition to recapitulating experimental flow patterns, our model explains observations that remained elusive, and makes a series of new predictions. First, the model captures the vorticity of cytosolic flows, which highlights deviations from Stokes' flow that were observed experimentally but remained unexplained. Second, the model reveals strong differences in the gel and cytosol motion. In particular, a micron-sized boundary layer is predicted close to the cortex, where the gel slides tangentially whilst the cytosolic flow cannot slip. Third, the model unveils a mechanism that stabilizes the spreading of nuclei with respect to perturbations of their initial positions. This self-correcting mechanism is argued to be functionally important for proper nuclear spreading. Fourth, we use our model to analyze the effects of flows on the transport of the morphogen Bicoid, and the establishment of its gradients. Finally, the model predicts that the flow strength should be reduced if the shape of the domain is more round, which is experimentally confirmed inDrosophilamutants. Thus, our two-fluid model explains flows and nuclear positioning in earlyDrosophila, while making predictions that suggest novel future experiments.

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“…Accurate control of nuclear density at the embryo surface plays a crucial role in the decision whether nuclei divide or not prior to the maternal-to-zygotic transition (MZT). This decision is made collectively by nuclei [28]. Yet, fluctuations of about 20-30% in local nuclear density could be sufficient to generate a variable number of divisions in different regions of the embryo [38].…”

Section: Introductionmentioning

confidence: 99%

Scale-independent topological interactions drive the first fate decision in theDrosophilaembryo

Hur,

Mukherjee,

Hayden

et al. 2023

Preprint

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During embryogenesis, the earliest cell fate decision is often linked to nuclear positioning, whose control arises from the integration of the cell cycle oscillator and associated cytoskeletal dynamics. Yet, the mechanisms that ensure that the correct number of nuclei move to the appropriate place remain poorly understood. Here, using light sheet microscopy, we show that in Drosophila embryos spindle orientation controls which nuclei migrate towards the cortex and which remains inside the embryo, thereby determining nuclear fate and the number of cells undergoing development. Combining computational methods inspired by integral geometry and manipulations of cell cycle genes, we show that spindle orientation is controlled by topological spindle-spindle interactions and not by internuclear distance. Using arguments describing the behavior of space-filling systems, we develop a theory for topological dependency in microtubule structures. Our work shows how topological interplay of microtubule mechanics can ensure robust control of density and cell fate determination.

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Cullin-5 mutants reveal collective sensing of the nucleocytoplasmic ratio in Drosophila embryogenesis

Cited by 10 publications

References 57 publications

The nuclear to cytoplasmic ratio drives cellularization in the close animal relativeSphaeroforma arctica

The nuclear to cytoplasmic ratio drives cellularization in the close animal relativeSphaeroforma arctica

Two-fluid dynamics and micron-thin boundary layers shape cytoplasmic flows in earlyDrosophilaembryos

Scale-independent topological interactions drive the first fate decision in theDrosophilaembryo

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