The majority of animals show external bilateral symmetry, precluding the observation of multiple internal left-right (L/R) asymmetries that are fundamental for organ packaging and function1,2. In vertebrates, left identity is mediated by the left-specific Nodal-Pitx2 axis that is repressed on the right-hand side by the epithelial-mesenchymal transition (EMT) inducer Snail13,4. Despite some existing evidence3,5, it remains unclear whether an equivalent instructive pathway provides right-hand specific information to the embryo. Here we show that in zebrafish, BMP mediates the L/R asymmetric activation of another EMT inducer, Prrx1a, in the lateral plate mesoderm (LPM) with higher levels on the right. Prrx1a drives L/R differential cell movements towards the midline leading to a leftward displacement of the cardiac posterior pole through an actomyosin-dependent mechanism. Downregulation of Prrx1a prevents heart looping and leads to mesocardia. Two parallel and mutually repressed pathways, respectively driven by Nodal and BMP on the left and right LPM, converge on the asymmetric activation of Pitx2 and Prrx1, two transcription factors that integrate left and right information to govern heart morphogenesis. This mechanism is conserved in the chicken embryo and, in the mouse, Snail1 fulfills the role played by Prrx1 in fish and chick. Thus, a differential L/R EMT produces asymmetric cell movements and forces, more prominent from the right, that drive heart laterality in vertebrates.
The authors regret that Table 2 of the article (ZENETOS et al., 2011) contained some errors. The errors pertain to nomenclature changes and the distribution/establishment success of alien species in the Mediterranean MSFD areas.
The state-of-art on alien species in the Mediterranean Sea is presented, making distinctions among the four subregions defined in the EU Marine Strategy Framework Directive: (i) the Western Mediterranean Sea (WMED); (ii) the Central Mediterranean Sea (CMED); (iii) the Adriatic Sea (ADRIA); and (iv) the Eastern Mediterranean Sea (EMED). The updated checklist (December 2010) of marine alien species within each subregion, along with their acclimatization status and origin, is provided. A total of 955 alien species is known in the Mediterranean, the vast majority of them having being introduced in the EMED (718), less in the WMED (328) and CMED (267) and least in the Adriatic (171). Of these, 535 species (56%) are established in at least one area. Despite the collective effort of experts who attempted in this work, the number of introduced species remains probably underestimated. Excluding microalgae, for which knowledge is still insufficient, aliens have increased the total species richness of the Mediterranean Sea by 5.9%. This figure should not be directly read as an indication of higher biodiversity, as spreading of so many aliens within the basin is possibly causing biotic homogenization. Thermophilic species, i.e. Indo-Pacific, Indian Ocean, Red Sea, Tropical Atlantic, Tropical Pacific, and circum(sub)tropical, account for 88.4% of the introduced species in the EMED, 72.8% in the CMED, 59.3% in the WMED and 56.1% in the Adriatic. Cold water species, i.e. circumboreal, N Atlantic, and N Pacific, make up a small percentage of the introduced species, ranging between 4.2% and 21.6% and being more numerous in the Adriatic and less so in the EMED. Species that are classified as invasive or potentially invasive are 134 in the whole of the Mediterranean: 108 are present in the EMED, 76 in the CMED, 53 in the Adriatic and 64 in the WMED. The WMED hosts most invasive macrophytes, whereas the EMED has the lion's share in polychaetes, crustaceans, molluscs and fish.
Anthropogenic climate change, and global warming in particular, has strong and increasing impacts on marine ecosystems (Poloczanska et al., 2013; Halpern et al., 2015; Smale et al., 2019). The Mediterranean Sea is considered a marine biodiversity hot-spot contributing to more than 7% of world's marine biodiversity including a high percentage of endemic species (Coll et al., 2010). The Mediterranean region is a climate change hotspot, where the respective impacts of warming are very pronounced and relatively well documented (Cramer et al., 2018). One of the major impacts of sea surface temperature rise in the marine coastal ecosystems is the occurrence of mass mortality events (MMEs). The first evidences of this phenomenon dated from the first half of'80 years affecting the Western Mediterranean and the Aegean Sea (Harmelin, 1984; Bavestrello and Boero, 1986; Gaino and Pronzato, 1989; Voultsiadou et al., 2011). The most impressive phenomenon happened in 1999 when an unprecedented large scale MME impacted populations of more than 30 species from different phyla along the French and Italian coasts (Cerrano et al., 2000; Perez et al., 2000). Following this event, several other large scale MMEs have been reported, along with numerous other minor ones, which are usually more restricted in geographic extend and/or number of affected species (Garrabou et al., 2009; Rivetti et al., 2014; Marbà et al., 2015; Rubio-Portillo et al., 2016, authors' personal observations). These events have generally been associated with strong and recurrent marine heat waves (Crisci et al., 2011; Kersting et al., 2013; Turicchia et al., 2018; Bensoussan et al., 2019) which are becoming more frequent globally (Smale et al., 2019). Both field observations and future projections using Regional Coupled Models (Adloff et al., 2015; Darmaraki et al., 2019) show the increase in Mediterranean sea surface temperature, with more frequent occurrence of extreme ocean warming events. As a result, new MMEs are expected during the coming years. To date, despite the efforts, neither updated nor comprehensive information can support scientific analysis of mortality events at a Mediterranean regional scale. Such information is vital to guide management and conservation strategies that can then inform adaptive management schemes that aim to face the impacts of climate change. ; Funding. MV-L was supported by a postdoctoral contract Juan de la Cierva-Incorporación (IJCI-2016-29329) of Ministerio de Ciencia, Innovación y Universidades. AI was supported by a Technical staff contract (PTA2015-10829-I) Ayudas Personal Técnico de Apoyo of Ministerio de Economía y Competitividad (2015). Interreg Med Programme (grant number Project MPA-Adapt 1MED15_3.2_M2_337) 85% cofunded by the European Regional Development Fund, the MIMOSA project funded by the Foundation Prince Albert II Monaco and the European Union's Horizon 2020 research and innovation programme under grant agreement no 689518 (MERCES). DG-G was supported by an FPU grant (FPU15/05457) from the Spanish Ministry of Education. J-BL was partially supported by the Strategic Funding UID/Multi/04423/2013 through national funds provided by FCT - Foundation for Science and Technology and European Regional Development Fund (ERDF), in the framework of the programme PT2020.
