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This is a textbook on modelling, data analysis and numerical techniques for advanced students and researchers in chemical, biological, geological and physical oceanography.

Embryonic stem (ES) cells can undergo many aspects of mammalian embryogenesis in vitro 1 – 5 , but their developmental potential is substantially extended by interactions with extraembryonic stem cells, including trophoblast stem (TS) cells, extraembryonic endoderm stem (XEN) cells and inducible XEN (iXEN) cells 6 – 11 . Here we assembled stem cell-derived embryos in vitro from mouse ES cells, TS cells and iXEN cells and showed that they recapitulate the development of whole natural mouse embryo in utero up to day 8.5 post-fertilization. Our embryo model displays headfolds with defined forebrain and midbrain regions and develops a beating heart-like structure, a trunk comprising a neural tube and somites, a tail bud containing neuromesodermal progenitors, a gut tube, and primordial germ cells. This complete embryo model develops within an extraembryonic yolk sac that initiates blood island development. Notably, we demonstrate that the neurulating embryo model assembled from Pax6 -knockout ES cells aggregated with wild-type TS cells and iXEN cells recapitulates the ventral domain expansion of the neural tube that occurs in natural, ubiquitous Pax6 -knockout embryos. Thus, these complete embryoids are a powerful in vitro model for dissecting the roles of diverse cell lineages and genes in development. Our results demonstrate the self-organization ability of ES cells and two types of extraembryonic stem cells to reconstitute mammalian development through and beyond gastrulation to neurulation and early organogenesis. Synthetic mouse embryos assembled from embryonic stem cells, trophoblast stem cells and induced extraembryonic endoderm stem cells closely recapitulate the development of wild-type and mutant natural mouse embryos up to embryonic day 8.5.

Mammalian embryos sequentially differentiate into trophectoderm and an inner cell mass, the latter of which differentiates into primitive endoderm and epiblast. Trophoblast stem (TS), extraembryonic endoderm (XEN) and embryonic stem (ES) cells derived from these three lineages can self-assemble into synthetic embryos, but the mechanisms remain unknown. Here, we show that a stem cell-specific cadherin code drives synthetic embryogenesis. The XEN cell cadherin code enables XEN cell sorting into a layer below ES cells, recapitulating the sorting of epiblast and primitive endoderm before implantation. The TS cell cadherin code enables TS cell sorting above ES cells, resembling extraembryonic ectoderm clustering above epiblast following implantation. Whereas differential cadherin expression drives initial cell sorting, cortical tension consolidates tissue organization. By optimizing cadherin code expression in different stem cell lines, we tripled the frequency of correctly formed synthetic embryos. Thus, by exploiting cadherin codes from different stages of development, lineage-specific stem cells bypass the preimplantation structure to directly assemble a postimplantation embryo. Bao et al. report that a cadherin code regulates the assembly and sorting of the first three cell lineages during mammalian development and can be manipulated to enhance the efficiency of synthetic embryogenesis.

Climate change is altering oceanic conditions in a complex manner, and the concurrent amendment of multiple properties will modify environmental stress for primary producers. So far, global modelling studies have focused largely on how alteration of individual properties will affect marine life. Here, we use global modelling simulations in conjunction with rotated factor analysis to express model projections in terms of regional trends in concomitant changes to biologically influential multi-stressors. Factor analysis demonstrates that regionally distinct patterns of complex oceanic change are evident globally. Preliminary regional assessments using published evidence of phytoplankton responses to complex change reveal a wide range of future responses to interactive multi-stressors with <20–300% shifts in phytoplankton physiological rates, and many unexplored potential interactions. In a future ocean, provinces will encounter different permutations of change that will probably alter the dominance of key phytoplankton groups and modify regional productivity, ecosystem structure and biogeochemistry. Consideration of regionally distinct multi-stressor patterns can help guide laboratory and field studies as well as the interpretation of interactive multi-stressors in global models. Modelling studies of climate change impacts on phytoplankton typically consider individual properties, which ignores the complex nature of the marine environment. This work undertakes regional assessments using multiple properties, including interactions, and finds shifts of <20–300% in phytoplankton physiological rates.

As daughter centrioles assemble during G2, they recruit conserved Ana3/RTTN followed by its partner Rcd4/PPP1R35. Together, this contributes to the subsequent recruitment of Ana1/CEP295, required for the centriole’s conversion to a centrosome. Here, we show that Rcd4/PPP1R35 is also required to maintain 9-fold centriole symmetry in the Drosophila male germline; its absence causes microtubule triplets to disperse into a reduced number of doublet or singlet microtubules. rcd4 -null mutant spermatocytes display skinny centrioles that elongate normally and localize centriolar components correctly. Mutant spermatocytes also have centrioles of normal girth that splay at their proximal ends when induced to elongate by Ana1 overexpression. Skinny and splayed spermatid centrioles can still recruit a proximal centriole-like (PCL) structure marking a capability to initiate features of centriole duplication in developing sperm. Thus, stable 9-fold symmetry of microtubule triplets is not essential for centriole growth, correct longitudinal association of centriole components, and aspects of centriole duplication. In this study, the authors show that centriole 9-fold microtubule symmetry is not essential for centriole elongation, correct distribution of the centriole’s components along its length, and in initiating aspects of centriole duplication.

On the scaffold Centrioles, cellular organelles composed of cylindrical arrays of nine microtubules, are essential for the formation of cilia, flagella and the centrosomes that organize microtubule structures within animal cells. Abnormal regulation of centriole duplication can lead to cancers and a number of ciliary diseases, and the centriolar protein Plk4 (Polo-like-kinase 4) is known to be a key regulator of centriole assembly. Now, David Glover and colleagues identify a single centriolar component, Asterless, as a scaffold for the binding of both Plk4 and another protein essential for centriole formation, Sas-4, with a key role in promoting centriole duplication. Centrioles are essential for the formation of centrosomes, cilia and flagella. The centriolar protein Polo-like-kinase 4 (Plk4) is a key regulator of centriole biogenesis and for maintaining constant centriole number in cells. These authors show that the centriolar protein Asterless (CEP152 in humans) interacts with Plk4 and Sas-4. They find that Asl functions as a scaffold for Plk4 and Sas-4 that facilitates self-assembly and duplication of the centriole, and organization of pericentriolar material. Centrioles are found in the centrosome core and, as basal bodies, at the base of cilia and flagella. Centriole assembly and duplication is controlled by Polo-like-kinase 4 (Plk4): these processes fail if Plk4 is downregulated and are promoted by Plk4 overexpression 1 , 2 , 3 , 4 , 5 , 6 , 7 . Here we show that the centriolar protein Asterless (Asl; human orthologue CEP152) provides a conserved molecular platform, the amino terminus of which interacts with the cryptic Polo box of Plk4 whereas the carboxy terminus interacts with the centriolar protein Sas-4 (CPAP in humans). Drosophila Asl and human CEP152 are required for the centrosomal loading of Plk4 in Drosophila and CPAP in human cells, respectively. Depletion of Asl or CEP152 caused failure of centrosome duplication; their overexpression led to de novo centriole formation in Drosophila eggs, duplication of free centrosomes in Drosophila embryos, and centrosome amplification in cultured Drosophila and human cells. Overexpression of a Plk4-binding-deficient mutant of Asl prevented centriole duplication in cultured cells and embryos. However, this mutant protein was able to promote microtubule organizing centre (MTOC) formation in both embryos and oocytes. Such MTOCs had pericentriolar material and the centriolar protein Sas-4, but no centrioles at their core. Formation of such acentriolar MTOCs could be phenocopied by overexpression of Sas-4 in oocytes or embryos. Our findings identify independent functions for Asl as a scaffold for Plk4 and Sas-4 that facilitates self-assembly and duplication of the centriole and organization of pericentriolar material.

A crucial question in mammalian development is how cells of the early embryo differentiate into distinct cell types. The first decision is taken when cells undertake waves of asymmetric division that generate one daughter on the inside and one on the outside of the embryo. After this division, some cells on the inside remain pluripotent and give rise to the epiblast, and hence the future body, whereas others develop into the primitive endoderm, an extraembryonic tissue. How the fate of these inside cells is decided is unknown: Is the process random, or is it related to their developmental origins? To address this question, we traced all cells by live-cell imaging in intact, unmanipulated embryos until the epiblast and primitive endoderm became distinct. This analysis revealed that inner cell mass (ICM) cells have unrestricted developmental potential. However, cells internalized by the first wave of asymmetric divisions are biased toward forming pluripotent epiblast, whereas cells internalized in the next two waves of divisions are strongly biased toward forming primitive endoderm. Moreover, we show that cells internalized by the second wave up-regulate expression of Gata6 and Sox17, and changing the expression of these genes determines whether the cells become primitive endoderm. Finally, with our ability to determine the origin of cells, we find that inside cells that are mispositioned when they are born can sort into the correct layer. In conclusion, we propose a model in which the timing of cell internalization, cell position, and cell sorting combine to determine distinct lineages of the preimplantation mouse embryo.

Mammalian oocytes are notoriously prone to chromosome segregation errors leading to aneuploidy. The spindle provides the machinery for accurate chromosome segregation during cell division. Mammalian oocytes lack centrioles and, therefore, mouse meiotic spindle relies on the organization of numerous acentriolar microtubule organizing centers into two poles (polar microtubule organizing centers, pMTOCs). The traditional view is that, in mammalian oocytes, microtubules are the sole cytoskeletal component responsible for regulating pMTOC organization and spindle assembly. We identify a previously unrecognized F-actin pool that surrounds pMTOCs, forming F-actin cage-like structure. We demonstrate that F-actin localization on the spindle depends on unconventional myosins X and VIIb. Selective disruption of spindle-localized F-actin, using myosin X/VIIb knockdown oocytes or photoswitchable Optojasp-1, perturbs pMTOC organization, leading to unfocused spindle poles and chromosome missegregation. Here, we unveil an important function of spindle-localized F-actin in regulating pMTOC organization, a critical process for ensuring the fidelity of meiotic spindle formation and proper chromosome segregation. Errors in oocyte division can cause infertility and birth defects. Here, authors combine a genetic strategy with a novel optochemical tool to show that spindle pole-localized F-actin is essential for proper meiotic spindle assembly and chromosome segregation.

The coordinated activities at centromeres of two key cell cycle kinases, Polo and Aurora B, are critical for ensuring that the two sister kinetochores of each chromosome are attached to microtubules from opposite spindle poles prior to chromosome segregation at anaphase. Initial attachments of chromosomes to the spindle involve random interactions between kinetochores and dynamic microtubules, and errors occur frequently during early stages of the process. The balance between microtubule binding and error correction (e.g., release of bound microtubules) requires the activities of Polo and Aurora B kinases, with Polo promoting stable attachments and Aurora B promoting detachment. Our study concerns the coordination of the activities of these two kinases in vivo. We show that INCENP, a key scaffolding subunit of the chromosomal passenger complex (CPC), which consists of Aurora B kinase, INCENP, Survivin, and Borealin/Dasra B, also interacts with Polo kinase in Drosophila cells. It was known that Aurora A/Bora activates Polo at centrosomes during late G2. However, the kinase that activates Polo on chromosomes for its critical functions at kinetochores was not known. We show here that Aurora B kinase phosphorylates Polo on its activation loop at the centromere in early mitosis. This phosphorylation requires both INCENP and Aurora B activity (but not Aurora A activity) and is critical for Polo function at kinetochores. Our results demonstrate clearly that Polo kinase is regulated differently at centrosomes and centromeres and suggest that INCENP acts as a platform for kinase crosstalk at the centromere. This crosstalk may enable Polo and Aurora B to achieve a balance wherein microtubule mis-attachments are corrected, but proper attachments are stabilized allowing proper chromosome segregation.

Ocean acidification, the progressive change in ocean chemistry caused by uptake of atmospheric CO2, is likely to affect some marine resources negatively, including shellfish. The Atlantic sea scallop (Placopecten magellanicus) supports one of the most economically important single-species commercial fisheries in the United States. Careful management appears to be the most powerful short-term factor affecting scallop populations, but in the coming decades scallops will be increasingly influenced by global environmental changes such as ocean warming and ocean acidification. In this paper, we describe an integrated assessment model (IAM) that numerically simulates oceanographic, population dynamic, and socioeconomic relationships for the U.S. commercial sea scallop fishery. Our primary goal is to enrich resource management deliberations by offering both short- and long-term insight into the system and generating detailed policy-relevant information about the relative effects of ocean acidification, temperature rise, fishing pressure, and socioeconomic factors on the fishery using a simplified model system. Starting with relationships and data used now for sea scallop fishery management, the model adds socioeconomic decision making based on static economic theory and includes ocean biogeochemical change resulting from CO2 emissions. The model skillfully reproduces scallop population dynamics, market dynamics, and seawater carbonate chemistry since 2000. It indicates sea scallop harvests could decline substantially by 2050 under RCP 8.5 CO2 emissions and current harvest rules, assuming that ocean acidification affects P. magellanicus by decreasing recruitment and slowing growth, and that ocean warming increases growth. Future work will explore different economic and management scenarios and test how potential impacts of ocean acidification on other scallop biological parameters may influence the social-ecological system. Future empirical work on the effect of ocean acidification on sea scallops is also needed.