Developmental Dynamics最新文献

Background: CD163 is a scavenger receptor predominantly expressed on the surfaces of macrophages in various mammalian species and is a marker of anti-inflammatory (M2-like) macrophages. High density of CD163-positive tumor-associated macrophages (TAMs) is associated with worse prognosis in various patient tumors. Interestingly, studies on mice have shown that CD163-positive TAMs only infiltrate the margins of tumor tissues, not the center. Based on these observations, we hypothesized that circulating monocyte-derived macrophages (MDMs), which are the origin of most TAMs, do not express CD163 in mice.

Results: We examined CD163 expression in MDMs, differentiated from healthy animals in vitro, and in normal, pathogenic, and tumorigenic macrophages infiltrating various tumors and organs across multiple species including primates, rodents, cetartiodactylans, and carnivores. We found that MDMs, including TAMs, do not express CD163 in mice. Our findings also suggest that murine CD163-positive macrophages likely originate from a specific subset of resident macrophages, namely fetal liver monocytes/macrophages, as indicated by fetal analysis. Furthermore, we revealed that the CD163-negative expression pattern in MDMs is a trait shared by the rodent clade.

Conclusions: Rodent MDMs do not express CD163, a phenotype not shared with MDMs of other mammals. Our findings caution against the extrapolation of rodent experimental results to other animal models.

Background: Craniofacial and trunk skeletal muscles are derived from different progenitor populations during development. Trunk skeletal muscles contain mostly multinucleated myofibers that are formed through myoblast fusion. However, myoblast fusion in craniofacial muscles and its molecular regulation are not well understood. Recent studies revealed that genetic mutations in MYOMAKER and MYOMIXER fusogens in humans cause Carey-Fineman-Ziter Syndrome (CFZS), characterized by facial weakness and lower jaw deformity.

Results: Previous studies in zebrafish revealed that knockout of myomaker and myomixer resulted in deformed craniofacial formation. To establish the causal connection between loss of fusogen function and craniofacial deformities, we characterized myoblast fusion in zebrafish craniofacial muscles. Our results demonstrate that myomaker and myomixer are expressed in both slow and fast craniofacial muscles, and loss of these fusogens results in defects in craniofacial myoblast fusion. Interestingly, unlike trunk muscles of early embryos and larvae that show fast-fiber-specific fusogen expression and fusion while slow muscle fusion only occurs at 3 weeks post-fertilization, both slow and fast craniofacial muscles fuse as early as 3 days post-fertilization.

Conclusions: Collectively, this study demonstrates that myomaker and myomixer are expressed in both slow and fast-twitch craniofacial muscles and are essential for myoblast fusion and the development of craniofacial muscles.

Gfi1 plays an important role in the development of hair cells (HCs), as indicated by its ability to regulate the expression of HC-related genes while the organ of Corti is developing. Given that the HCs and the supporting cells (SCs) are coming from a common stem/progenitor cell pool, it is conceivable to regenerate HCs from SCs that ectopically express Gfi1. The focus of this review was to elucidate the role of Gfi1 in controlling the development of HCs by dissecting the phenotypes of the inner ear in Gfi1-mutated mouse lines. In addition, we reviewed studies of regeneration in the mammalian inner ear, by which we discussed the novel function of Gfi1 as an essential factor in guiding non-HCs toward an HC destiny in coordination with Atoh1 and Pou4f3. Finally, we summarized the known Gfi1-specific Cre/CreER/reporter mouse lines and highlighted the pros and cons of each line, with the aim of providing insights for use in future studies. In summary, a better understanding of Gfi1 and its diverse roles is beneficial for advancing studies of HC regeneration in the inner ear.