Transcription Factors of the Alx Family: Evolutionarily Conserved Regulators of Deuterostome Skeletogenesis

Khor, Jian Ming; Ettensohn, Charles A.

doi:10.3389/fgene.2020.569314

Cited by 24 publications

(22 citation statements)

References 160 publications

(214 reference statements)

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“…Alx1 and Alx4 are paralogs that arose early in echinoderm evolution through gene duplication (11,24,25). The two proteins have almost identical HDs (97% amino acid identity) and share a highly conserved otp/aristaless/rax (OAR) domain but are otherwise dissimilar in sequence.…”

Section: Evolution Of Alx1 and The Role Of The D2 Domainmentioning

confidence: 99%

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Analysis of the DNA-binding properties of Alx1, an evolutionarily conserved regulator of skeletogenesis in echinoderms

Guerrero-Santoro

Khor

Açıkbaş

et al. 2021

Journal of Biological Chemistry

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Section: Evolution Of Alx1 and The Role Of The D2 Domainmentioning

confidence: 99%

“…Thus, alx1-related genes have a conserved role in the control of biomineral formation across chordates (24).…”

Section: Introductionmentioning

confidence: 99%

Analysis of the DNA-binding properties of Alx1, an evolutionarily conserved regulator of skeletogenesis in echinoderms

Guerrero-Santoro

Khor

Açıkbaş

et al. 2021

Journal of Biological Chemistry

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“…De novo motif analysis of these sets of enhancers using HOMER revealed distinct patterns of enriched motifs; more significantly, each set was enriched in motifs associated with cell type–specific TFs known to have important regulatory functions in the GRN deployed in that particular lineage ( Table 1 ). Thus, eRNA peaks located near genes differentially expressed by PMCs were enriched in motifs that matched binding sites for Ets1 and Alx1, two key early TFs in the skeletogenic GRN ( Kurokawa and Ettensohn 1999 ; Ettensohn et al 2003 ; Khor and Ettensohn 2020 ), whereas those located near genes differentially expressed by pigment cells showed an enrichment of consensus binding sites for Gcm, a pivotal regulator of pigment cell specification ( Ransick and Davidson 2006 ; Wessel et al 2020 ). Similarly, eRNA peaks located near genes differentially expressed in the ciliated band were enriched in consensus binding sites for Hnf6 ( Otim et al 2004 ), a component of the ciliary band GRN.…”

Section: Resultsmentioning

confidence: 99%

Global patterns of enhancer activity during sea urchin embryogenesis assessed by eRNA profiling

et al. 2021

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We used capped analysis of gene expression with sequencing (CAGE-seq) to profile eRNA expression and enhancer activity during embryogenesis of a model echinoderm: the sea urchin, Strongylocentrotus purpuratus. We identified more than 18,000 enhancers that were active in mature oocytes and developing embryos and documented a burst of enhancer activation during cleavage and early blastula stages. We found that a large fraction (73.8%) of all enhancers active during the first 48 h of embryogenesis were hyperaccessible no later than the 128-cell stage and possibly even earlier. Most enhancers were located near gene bodies, and temporal patterns of eRNA expression tended to parallel those of nearby genes. Furthermore, enhancers near lineage-specific genes contained signatures of inputs from developmental gene regulatory networks deployed in those lineages. A large fraction (60%) of sea urchin enhancers previously shown to be active in transgenic reporter assays was associated with eRNA expression. Moreover, a large fraction (50%) of a representative subset of enhancers identified by eRNA profiling drove tissue-specific gene expression in isolation when tested by reporter assays. Our findings provide an atlas of developmental enhancers in a model sea urchin and support the utility of eRNA profiling as a tool for enhancer discovery and regulatory biology. The data generated in this study are available at Echinobase, the public database of information related to echinoderm genomics.

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“…The transition between the secretion of Col2 in chondrocytes to Col1 in osteoblasts is regulated by a switch from a GRN dominated by Sox transcription factors to a GRN dominated by Runx’s ( Figure 4 C, [ 34 , 125 , 128 ]). In the proliferating chondrocytes the transcription factor, Sox9 is expressed in high levels together with Sox5, Sox6, Cart1 (homolog of Alx1 [ 129 ]) and the signaling receptor FGFR3 [ 34 , 121 , 130 ]. These regulatory genes drive the expression of Col2, as well as the expression of the cartilage proteoglycan, aggrecan (ACAN) and proteins from the small leucine-rich repeat proteoglycan (SLRP) family, Decorin and Biglycan [ 31 ].…”

Section: Grns That Drive Biomineralization In Vertebratesmentioning

confidence: 99%

The Evolution of Biomineralization through the Co-Option of Organic Scaffold Forming Networks

de-Leon

2022

Cells

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Biomineralization is the process in which organisms use minerals to generate hard structures like teeth, skeletons and shells. Biomineralization is proposed to have evolved independently in different phyla through the co-option of pre-existing developmental programs. Comparing the gene regulatory networks (GRNs) that drive biomineralization in different species could illuminate the molecular evolution of biomineralization. Skeletogenesis in the sea urchin embryo was extensively studied and the underlying GRN shows high conservation within echinoderms, larval and adult skeletogenesis. The organic scaffold in which the calcite skeletal elements form in echinoderms is a tubular compartment generated by the syncytial skeletogenic cells. This is strictly different than the organic cartilaginous scaffold that vertebrates mineralize with hydroxyapatite to make their bones. Here I compare the GRNs that drive biomineralization and tubulogenesis in echinoderms and in vertebrates. The GRN that drives skeletogenesis in the sea urchin embryo shows little similarity to the GRN that drives bone formation and high resemblance to the GRN that drives vertebrates’ vascular tubulogenesis. On the other hand, vertebrates’ bone-GRNs show high similarity to the GRNs that operate in the cells that generate the cartilage-like tissues of basal chordate and invertebrates that do not produce mineralized tissue. These comparisons suggest that biomineralization in deuterostomes evolved through the phylum specific co-option of GRNs that control distinct organic scaffolds to mineralization.

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Transcription Factors of the Alx Family: Evolutionarily Conserved Regulators of Deuterostome Skeletogenesis

Cited by 24 publications

References 160 publications

Analysis of the DNA-binding properties of Alx1, an evolutionarily conserved regulator of skeletogenesis in echinoderms

Analysis of the DNA-binding properties of Alx1, an evolutionarily conserved regulator of skeletogenesis in echinoderms

Global patterns of enhancer activity during sea urchin embryogenesis assessed by eRNA profiling

The Evolution of Biomineralization through the Co-Option of Organic Scaffold Forming Networks

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