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Front Genet
2020 Apr 30;11:569314. doi: 10.3389/fgene.2020.569314.
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Transcription Factors of the Alx Family: Evolutionarily Conserved Regulators of Deuterostome Skeletogenesis.
Khor JM
,
Ettensohn CA
.
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Members of the alx gene family encode transcription factors that contain a highly conserved Paired-class, DNA-binding homeodomain, and a C-terminal OAR/Aristaless domain. Phylogenetic and comparative genomic studies have revealed complex patterns of alx gene duplications during deuterostome evolution. Remarkably, alx genes have been implicated in skeletogenesis in both echinoderms and vertebrates. In this review, we provide an overview of current knowledge concerning alx genes in deuterostomes. We highlight their evolutionarily conserved role in skeletogenesis and draw parallels and distinctions between the skeletogenic gene regulatory circuitries of diverse groups within the superphylum.
Figure 2. Activation of Alx1 in euechinoids (S. purpuratus) and regulatory inputs into primary mesenchyme cell (PMC) effector genes. Only a small number of more than 420 effector genes differentially expressed in PMCs (Rafiq et al., 2014) is shown here. A large subset of effector genes receives regulatory inputs from both Ets1 and Alx1 (Rafiq et al., 2014). Positive regulatory inputs by Ets1 and Alx1 into msp130, sm50, and vegf-Ig-10 are described in (Oliveri et al., 2008). Direct targets of the sea urchin Alx1 (Khor et al., 2019) define a genetic subcircuit that impinges on almost all aspect of PMC morphogenesis, including directional cell migration, extracellular matrix (ECM) remodeling, cell-cell fusion, and biomineralization. Dashed arrows indicate interactions that may be indirect. For additional information regarding the developmental functions of the specific effector genes shown here, see Shashikant et al. (2018) and references therein.