Molecular evolution of the EGF–CFC protein family

Ravisankar, V.; Singh, Taran P.

doi:10.1016/j.gene.2011.05.007

Cited by 12 publications

(12 citation statements)

References 74 publications

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“…In contrast, searches for Lefty orthologues were so far positive only in deuterostomes ( Chen and Schier, 2002 ; Mita and Fujiwara, 2007 ; Duboc et al, 2008 ; Li et al, 2017 ), but not in Lophotrochozoa ( Grande et al, 2014 ). Similarly, the Nodal coreceptor EGF-CFC has been identified only in deuterostomes ( Yan et al, 1999 ; Ravisankar et al, 2011 ), and FoxH1 orthologues have been characterised in vertebrates and cephalochordates only ( Weisberg et al, 1998 ; Zhou et al, 1998 ; Yu et al, 2008 ; Figure 5A ). Nodal-signalling components have not been identified in the protostome model organisms D. melanogaster and C. elegans .…”

Section: Resultsmentioning

confidence: 99%

The genetic factors of bilaterian evolution

Heger

Zheng

Rottmann

et al. 2020

eLife

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The Cambrian explosion was a unique animal radiation ~540 million years ago that produced the full range of body plans across bilaterians. The genetic mechanisms underlying these events are unknown, leaving a fundamental question in evolutionary biology unanswered. Using large-scale comparative genomics and advanced orthology evaluation techniques, we identified 157 bilaterian-specific genes. They include the entire Nodal pathway, a key regulator of mesoderm development and left-right axis specification; components for nervous system development, including a suite of G protein-coupled receptors that control physiology and behaviour, the Robo-Slit midline repulsion system, and the neurotrophin signalling system; a high number of zinc finger transcription factors; and novel factors that previously escaped attention. Contradicting the current view, our study reveals that genes with bilaterian origin are robustly associated with key features in extant bilaterians, suggesting a causal relationship.

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Section: Resultsmentioning

confidence: 99%

The genetic factors of bilaterian evolution

Heger

Zheng

Rottmann

et al. 2020

eLife

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“…Studies regarding asymmetric regulation of a number of signalling proteins, motor proteins and transcription factors involved in establishing this asymmetry have aided our understanding to some extent. Among the genes studied, the importance of the highly conserved EGF-CFC family of genes is yet to be realised [10, 23]. Probably through gene duplication and specification, the mammalian genome contains two of the EGF-CFC family members Cryptic and Cripto, each controlling different cellular functions [10, 23].…”

Section: Discussionmentioning

confidence: 99%

“…Among the genes studied, the importance of the highly conserved EGF-CFC family of genes is yet to be realised [10, 23]. Probably through gene duplication and specification, the mammalian genome contains two of the EGF-CFC family members Cryptic and Cripto, each controlling different cellular functions [10, 23]. Mutations detected have helped to conclude that ‘Cripto’ controls the anterior-posterior axis formation in mice, whereas the other member Cryptic, controls the L-R positioning of organs in humans indicating a divergence in the function of the two family members [10].…”

Section: Discussionmentioning

confidence: 99%

Left-right axis asymmetry determining human Cryptic gene is transcriptionally repressed by Snail

2016

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BackgroundEstablishment of the left-right axis is important for positioning organs asymmetrically in the developing vertebrate-embryo. A number of factors like maternally deposited molecules have emerged essential in initiating the specification of the axis; the downstream events, however, are regulated by signal-transduction and gene-expression changes identifying which remains a crucial challenge. The EGF-CFC family member Cryptic, that functions as a co-receptor for some TGF-beta ligands, is developmentally expressed in higher mammals and mutations in the gene cause loss or change in left-right axis asymmetry. Despite the strong phenotype, no transcriptional-regulator of this gene is known till date.ResultsUsing promoter-analyses tools, we found strong evidence that the developmentally essential transcription factor Snail binds to the human Cryptic-promoter. We cloned the promoter-region of human Cryptic in a reporter gene and observed decreased Cryptic-promoter activation upon increasing Snail expression. Further, the expression of Cryptic is down-regulated upon exogenous Snail expression, validating the reporter assays and the previously identified role of Snail as a transcriptional repressor. Finally, we demonstrate using gel-shift assay that Snail in nuclear extract of PANC1 cells interacts with the promoter-construct bearing putative Snail binding sites and confirm this finding using chromatin immunoprecipitation assay.ConclusionsSnail represses the expression of human Cryptic and therefore, might affect the signaling via Nodal that has previously been demonstrated to specify the left-right axis using the EGF-CFC co-receptors.

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“…The epidermal growth factor (EGF)-Cripto-1-FRL-1-Cryptic (CFC) family encompasses several members identified in deuterostomes, especially in vertebrates [ 6 ]. Human Cripto-1 is the founding member of this family and primarily functions during embryogenesis as a co-receptor for the transforming growth factor beta (TGF-β) family of ligands Nodal and growth and differentiation factors 1 and 3 (GDF-1, -3) in a canonical pathway, leading to the activation of the Activin type I (Alk4,7)/Activin type II (ActRII) receptor complex that subsequently triggers phosphorylation of Smad-2/Smad-3, and the activation of this Smad-dependent intracellular signaling pathway mediated by Smad-4 [ 7 ] (Fig.…”

Section: Cripto-1 Notch/csl and Wnt/β-catenin Signaling In Mammary mentioning

confidence: 99%

Developmental signaling pathways regulating mammary stem cells and contributing to the etiology of triple-negative breast cancer

Rangel

Bertolette

Castro

et al. 2016

Breast Cancer Res Treat

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Cancer has been considered as temporal and spatial aberrations of normal development in tissues. Similarities between mammary embryonic development and cell transformation suggest that the underlying processes required for mammary gland development are also those perturbed during various stages of mammary tumorigenesis and breast cancer (BC) development. The master regulators of embryonic development Cripto-1, Notch/CSL, and Wnt/β-catenin play key roles in modulating mammary gland morphogenesis and cell fate specification in the embryo through fetal mammary stem cells (fMaSC) and in the adult organism particularly within the adult mammary stem cells (aMaSC), which determine mammary progenitor cell lineages that generate the basal/myoepithelial and luminal compartments of the adult mammary gland. Together with recognized transcription factors and embryonic stem cell markers, these embryonic regulatory molecules can be inappropriately augmented during tumorigenesis to support the tumor-initiating cell (TIC)/cancer stem cell (CSC) compartment, and the effects of their deregulation may contribute for the etiology of BC, in particular the most aggressive subtype of BC, triple-negative breast cancer (TNBC). This in depth review will present evidence of the involvement of Cripto-1, Notch/CSL, and Wnt/β-catenin in the normal mammary gland morphogenesis and tumorigenesis, from fMaSC/aMaSC regulation to TIC generation and maintenance in TNBC. Specific therapies for treating TNBC by targeting these embryonic pathways in TICs will be further discussed, providing new opportunities to destroy not only the bulk tumor, but also TICs that initiate and promote the metastatic spread and recurrence of this aggressive subtype of BC.

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Molecular evolution of the EGF–CFC protein family

Cited by 12 publications

References 74 publications

The genetic factors of bilaterian evolution

The genetic factors of bilaterian evolution

Left-right axis asymmetry determining human Cryptic gene is transcriptionally repressed by Snail

Developmental signaling pathways regulating mammary stem cells and contributing to the etiology of triple-negative breast cancer

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