Volvox as a Model for Studying Cell Death and Senescence

The spherical green alga Volvox consists of several hundred or thousand of somatic cells that undergo terminal differentiation, senescence and death, and a small number of gonidia (asexual reproductive cells) that give rise to the next generation. In the first part of this paper, the ontogenetic diversity of the genus Volvox is briefly considered, as well as the mechanisms of differentiation into the two types of cells mentioned above, which have been thoroughly studied during recent years in Volvox carteri. Then, a detailed critical analysis of the literature and some of my own data on senescence and cell death (mainly in V. carteri and, to a lesser extent, in V. aureus) was carried out, and it was noted that this aspect of Volvox developmental biology has not been sufficiently studied. Some perspectives of further research of the processes of cell death and senescence in representatives of the genus Volvox in a comparative aspect are indicated.

Tissue-resident macrophages in the intestine are long lived and defined by Tim-4 and CD4 expression

A defining feature of resident gut macrophages is their high replenishment rate from blood monocytes attributed to tonic commensal stimulation of this site. In contrast, almost all other tissues contain locally maintained macrophage populations, which coexist with monocyte-replenished cells at homeostasis. In this study, we identified three transcriptionally distinct mouse gut macrophage subsets that segregate based on expression of Tim-4 and CD4. Challenging current understanding, Tim-4+CD4+ gut macrophages were found to be locally maintained, while Tim-4–CD4+ macrophages had a slow turnover from blood monocytes; indeed, Tim-4–CD4– macrophages were the only subset with the high monocyte-replenishment rate currently attributed to gut macrophages. Moreover, all macrophage subpopulations required live microbiota to sustain their numbers, not only those derived from blood monocytes. These findings oppose the prevailing paradigm that all macrophages in the adult mouse gut rapidly turn over from monocytes in a microbiome-dependent manner; instead, these findings supplant it with a model of ontogenetic diversity where locally maintained subsets coexist with rapidly replaced monocyte-derived populations.

Inflammation and Cancer: Extra- and Intracellular Determinants of Tumor-Associated Macrophages as Tumor Promoters

One of the hallmarks of cancer-related inflammation is the recruitment of monocyte-macrophage lineage cells to the tumor microenvironment. These tumor infiltrating myeloid cells are educated by the tumor milieu, rich in cancer cells and stroma components, to exert functions such as promotion of tumor growth, immunosuppression, angiogenesis, and cancer cell dissemination. Our review highlights the ontogenetic diversity of tumor-associated macrophages (TAMs) and describes their main phenotypic markers. We cover fundamental molecular players in the tumor microenvironment including extra- (CCL2, CSF-1, CXCL12, IL-4, IL-13, semaphorins, WNT5A, and WNT7B) and intracellular signals. We discuss how these factors converge on intracellular determinants (STAT3, STAT6, STAT1, NF-κB, RORC1, and HIF-1α) of cell functions and drive the recruitment and polarization of TAMs. Since microRNAs (miRNAs) modulate macrophage polarization key miRNAs (miR-146a, miR-155, miR-125a, miR-511, and miR-223) are also discussed in the context of the inflammatory myeloid tumor compartment. Accumulating evidence suggests that high TAM infiltration correlates with disease progression and overall poor survival of cancer patients. Identification of molecular targets to develop new therapeutic interventions targeting these harmful tumor infiltrating myeloid cells is emerging nowadays.

Heterochrony, dental ontogenetic diversity, and the circumvention of constraints in marsupial mammals and extinct relatives

In marsupial mammals and their extinct relatives—collectively, metatherians—only the last premolar is replaced, but the timing of dental eruption is variable within the group. Our knowledge of fossils metatherians is limited, but is critical to understanding several aspects of the evolution and morphological diversification of this clade. We analyzed the sequence of eruption of 76 specimens of metatherians, including Sparassodonta, an extinct clade of specialized carnivores from South America. In Sparassodonta (1) the P3/p3 erupt simultaneously, in common with some didelphids (in other didelphids, p3 erupts before P3, whereas in the remaining didelphids, some peramelids, one caenolestid, andPucadelphysthis order is reversed); (2) the upper and lower molars at the same locus erupt more in synchrony than in other carnivorous metatherians in which the lower molars clearly precede the upper equivalents; (3) the upper canine in thylacosmilids and proborhyaenids is hypselodont; (4) species with similar molar morphologies have different morphologies of the deciduous premolars, suggesting diverse diets among the juveniles of different taxa; (5) deciduous teeth are functional for a long period of time, with thylacosmilids even retaining a functional DP3 in the permanent dentition. The retention of the DP3 and the hypertrophied and hypselodont upper canine of thylacosmilids represent clear heterochronic shifts. Specializations in the timing of dental eruption and in the deciduous tooth shape of sparassodonts are evolutionary mechanisms that circumvent constraints imposed by the metatherian replacement pattern and increase morphological disparity during ontogeny.