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    An exclusive cellular and molecular network governs intestinal smooth muscle cell differentiation in vertebrates
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    Abstract:
    Intestinal smooth muscle cells (iSMCs) are a crucial component of the adult gastrointestinal tract and support intestinal differentiation, peristalsis and epithelial homeostasis during development. Despite these crucial roles, the origin of iSMCs and the mechanisms responsible for their differentiation and function remain largely unknown in vertebrates. Here, we demonstrate that iSMCs arise from the lateral plate mesoderm (LPM) in a stepwise process. Combining pharmacological and genetic approaches, we show that TGFβ/Alk5 signaling drives the LPM ventral migration and commitment to an iSMC fate. The Alk5-dependent induction of zeb1a and foxo1a is required for this morphogenetic process: zeb1a is responsible for driving LPM migration around the gut, whereas foxo1a regulates LPM predisposition to iSMC differentiation. We further show that TGFβ, zeb1a and foxo1a are tightly linked together by miR-145 In iSMC-committed cells, TGFβ induces the expression of miR-145, which in turn is able to downregulate zeb1a and foxo1a The absence of miR-145 results in only a slight reduction in the number of iSMCs, which still express mesenchymal genes but fail to contract. Together, our data uncover a cascade of molecular events that govern distinct morphogenetic steps during the emergence and differentiation of vertebrate iSMCs.
    Ferritins are ubiquitous, highly-conserved proteins that constitute one of the most important components of the cellular machinery devoted to the management of iron levels. Various ferritins have been described in vertebrates, though their exact functions and phylogenetic relationships remain to be established. Our attempts to properly annotate two ferritin subunits isolated from the Asian sea bass Lates calcarifer, prompted us to investigate the evolutionary relationships among vertebrate ferritins and their relationships with non-vertebrate homologs. We carried out a detailed screening of mined ferritin sequences by examining the regulatory elements and gene structures. Subsequently, we performed comprehensive phylogenetic analyses involving the various metazoan and vertebrate ferritin chain types, respectively. Our analyses suggest that a single ferritin chain duplicated in the early vertebrates and that the various ferritin chain types in vertebrate and non-vertebrate species evolved independently through lineage-specific duplications. Notably, this includes the mitochondrial ferritin found only in insects and mammals that we show to result from two parallel lineage-specific duplications followed by convergent events of mitochondrial targeting. Regarding the various cytosolic ferritin chains in vertebrates, our results suggest a scenario of a duplication at the base of vertebrates followed by more recent duplications in teleosts and amphibians. This scenario implies that the light chain in mammals is orthologous to the middle chain in teleosts, in contrast to previous claims of a paralogous relationship coupled with differential gene loss. We hypothesise that the extensive differences in sequence and function between these two orthologous chains may have been driven by the adaptation of tetrapods to terrestrial environments, which involved changes in the dynamics of iron uptake and storage. Altogether, our analyses clarify the evolutionary relationships among vertebrate ferritins and pave the way for the interpretation of functional adaptations within an evolutionary framework.
    Lineage (genetic)
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    Amphioxus or lancelet, a cephalochordate,is the extant invertebrate most closely related to the proximate ancestor of vertebrate, and has long been regarded as the model animal for insights into the evolution of vertebrate and the embryonic development. Its genetic information on gene sequence and expression pattern is now being widely used for interspecies comparative genome studies and developmental homology analysis. Given its distinct phylogenetic position and its unduplicated genome, amphioxus promises to be especially helpful in comparative genomics. By comparing the genome of amphioxus, invertebrates and vertebrates, we can unravel the genomic structure and evolutionary history of the vertebrate ancestor,which may give us an insight into the origin of the human being. Meanwhile, comparing the developmental genes expression pattern between the amphioxus and other animals can suggest body part homologies between distantly related species, and can help to understand how developmental genes lead to the morphological difference between them.
    Comparative Genomics
    Evolutionary developmental biology
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    The phylogenetic position of amphioxus, together with its relatively simple and evolutionarily conserved morphology and genome structure, has led to its use as a model for studies of vertebrate evolution. In particular, the recent development of technical approaches, as well as access to the complete amphioxus genome sequence, has provided the community with tools with which to study the invertebrate-chordate to vertebrate transition. Here, we present this animal model, discussing its life cycle, the model species studied and the experimental techniques that it is amenable to. We also summarize the major findings made using amphioxus that have informed us about the evolution of vertebrate traits.
    Chordate
    Evolutionary developmental biology
    Citations (136)