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Article: ADAM11 a novel regulator of Wnt and BMP4 signaling in neural crest and cancer.

Pandey, Ankit / Cousin, Hélène / Horr, Brett / Alfandari, Dominique

Frontiers in cell and developmental biology

2023 Volume 11, Page(s) 1271178

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-09-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1271178
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Article: ADAM11 a novel regulator of Wnt and BMP4 signaling in neural crest and cancer.

Pandey, Ankit / Cousin, Hélène / Horr, Brett / Alfandari, Dominique

bioRxiv : the preprint server for biology

2023

Abstract: Cranial neural crest (CNC) cells are induced at the border of the neural plate by a combination of FGF, Wnt, and BMP4 signaling. CNC then migrate ventrally and invade ventral structures where they contribute to craniofacial development. Here we show that ...

Abstract	Cranial neural crest (CNC) cells are induced at the border of the neural plate by a combination of FGF, Wnt, and BMP4 signaling. CNC then migrate ventrally and invade ventral structures where they contribute to craniofacial development. Here we show that a non-proteolytic ADAM, Adam11, originally identified as a putative tumor suppressor binds to proteins of the Wnt and BMP4 signaling pathway. Mechanistic studies concerning these non-proteolytic ADAM lack almost entirely. We show that Adam11 positively regulates BMP4 signaling while negatively regulating β-catenin activity. By modulating these pathways, Adam11 controls the timing of neural tube closure and the proliferation and migration of CNC. Using both human tumor data and mouse B16 melanoma cells, we further show that ADAM11 levels similarly correlate with Wnt or BMP4 activation levels. We propose that ADAM11 preserve naïve cells by maintaining low Sox3 and Snail/Slug levels through stimulation of BMP4 and repression of Wnt signaling, while loss of ADAM11 results in increased Wnt signaling, increased proliferation and early epithelium to mesenchyme transition.
Language	English
Publishing date	2023-06-13
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.13.544797
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Article: Zmym4 is required for early cranial gene expression and craniofacial cartilage formation.

Jourdeuil, Karyn / Neilson, Karen M / Cousin, Helene / Tavares, Andre L P / Majumdar, Himani D / Alfandari, Dominique / Moody, Sally A

Frontiers in cell and developmental biology

2023 Volume 11, Page(s) 1274788

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-10-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1274788
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Article ; Online: Cranial Neural Crest Explants.

Cousin, Hélène / Alfandari, Dominique

Cold Spring Harbor protocols

2018 Volume 2018, Issue 3

Abstract: The cranial neural crest (CNC) explant assay was originally designed to assess the basic requirements for CNC migration in vitro. This protocol describes the key parameters of CNC explants ... ...

Abstract	The cranial neural crest (CNC) explant assay was originally designed to assess the basic requirements for CNC migration in vitro. This protocol describes the key parameters of CNC explants in
MeSH term(s)	Animals ; Cattle ; Embryo, Nonmammalian/metabolism ; Neural Crest/physiology ; Skull/physiology ; Time-Lapse Imaging ; Tissue Culture Techniques/methods ; Xenopus laevis/embryology
Language	English
Publishing date	2018-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1559-6095
ISSN (online)	1559-6095
DOI	10.1101/pdb.prot097394
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Article ; Online: Cut loose and run: The complex role of ADAM proteases during neural crest cell development.

Alfandari, Dominique / Taneyhill, Lisa A

Genesis (New York, N.Y. : 2000)

2018 Volume 56, Issue 6-7, Page(s) e23095

Abstract: ADAM metalloproteases have been shown to play critical roles during development. In this review, we will describe functional evidence that implicates ADAM proteins during the genesis, migration and differentiation of neural crest cells. We will restrict ... ...

Abstract	ADAM metalloproteases have been shown to play critical roles during development. In this review, we will describe functional evidence that implicates ADAM proteins during the genesis, migration and differentiation of neural crest cells. We will restrict our analysis to the transmembrane ADAMs as other reviews have addressed the role of extracellular metalloproteases (Christian et al. [2013] Critical Reviews in Biochemistry and Molecular Biology 48:544-560). This review will describe advances that have been obtained mainly through the use of two vertebrate model systems, the frog, and avian embryos. The role of the principal substrates of ADAMs, the cadherins, has been extensively described in other reviews, most recently in (Cousin [1997] Mechanisms of Development 148:79-88; Taneyhill and Schiffmacher [2017] Genesis, 55). The function of ADAMs in the migration of other cell types, including the immune system, wound healing and cancer has been described previously in (Dreymueller et al. [2017] Mediators of Inflammation 2017: 9621724). Our goal is to illustrate both the importance of ADAMs in controlling neural crest behavior and how neural crest cells have helped us understand the molecular interactions, substrates, and functions of ADAM proteins in vivo.
MeSH term(s)	ADAM Proteins/metabolism ; ADAM Proteins/physiology ; Animals ; Cell Differentiation ; Cell Movement ; Humans ; Membrane Proteins/metabolism ; Neural Crest/embryology ; Neural Crest/metabolism ; Organogenesis ; Protein Transport ; Xenopus/metabolism ; Xenopus Proteins/metabolism
Chemical Substances	Membrane Proteins ; Xenopus Proteins ; ADAM Proteins (EC 3.4.24.-) ; ADAM19 protein, Xenopus (EC 3.4.24.-) ; ADAM33 protein, Xenopus (EC 3.4.24.-)
Language	English
Publishing date	2018-02-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2004544-X
ISSN	1526-968X ; 1526-954X
ISSN (online)	1526-968X
ISSN	1526-954X
DOI	10.1002/dvg.23095
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Article ; Online: Production and characterization of monoclonal antibodies to Xenopus proteins.

Horr, Brett / Kurtz, Ryan / Pandey, Ankit / Hoffstrom, Benjamin G / Schock, Elizabeth / LaBonne, Carole / Alfandari, Dominique

Development (Cambridge, England)

2023 Volume 150, Issue 4

Abstract: Monoclonal antibodies are powerful and versatile tools that enable the study of proteins in diverse contexts. They are often utilized to assist with identification of subcellular localization and characterization of the function of target proteins of ... ...

Abstract	Monoclonal antibodies are powerful and versatile tools that enable the study of proteins in diverse contexts. They are often utilized to assist with identification of subcellular localization and characterization of the function of target proteins of interest. However, because there can be considerable sequence diversity between orthologous proteins in Xenopus and mammals, antibodies produced against mouse or human proteins often do not recognize Xenopus counterparts. To address this issue, we refined existing mouse monoclonal antibody production protocols to generate antibodies against Xenopus proteins of interest. Here, we describe several approaches for the generation of useful mouse anti-Xenopus antibodies to multiple Xenopus proteins and their validation in various experimental approaches. These novel antibodies are now available to the research community through the Developmental Study Hybridoma Bank (DSHB).
MeSH term(s)	Animals ; Mice ; Antibodies, Monoclonal ; Hybridomas ; Xenopus laevis ; Xenopus Proteins/genetics
Chemical Substances	Antibodies, Monoclonal ; Xenopus Proteins
Language	English
Publishing date	2023-02-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.201309
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Article ; Online: Using Xenopus to discover new candidate genes involved in BOR and other congenital hearing loss syndromes.

Neal, Scott J / Rajasekaran, Anindita / Jusić, Nisveta / Taylor, Louis / Read, Mai / Alfandari, Dominique / Pignoni, Francesca / Moody, Sally A

Journal of experimental zoology. Part B, Molecular and developmental evolution

2023 Volume 342, Issue 3, Page(s) 212–240

Abstract: ... autosomal dominant congenital hearing loss syndromes is branchio-oto-renal syndrome (BOR), which also ...

Abstract	Hearing in infants is essential for brain development, acquisition of verbal language skills, and development of social interactions. Therefore, it is important to diagnose hearing loss soon after birth so that interventions can be provided as early as possible. Most newborns in the United States are screened for hearing deficits and commercially available next-generation sequencing hearing loss panels often can identify the causative gene, which may also identify congenital defects in other organs. One of the most prevalent autosomal dominant congenital hearing loss syndromes is branchio-oto-renal syndrome (BOR), which also presents with defects in craniofacial structures and the kidney. Currently, mutations in three genes, SIX1, SIX5, and EYA1, are known to be causative in about half of the BOR patients that have been tested. To uncover new candidate genes that could be added to congenital hearing loss genetic screens, we have combined the power of Drosophila mutants and protein biochemical assays with the embryological advantages of Xenopus, a key aquatic animal model with a high level of genomic similarity to human, to identify potential Six1 transcriptional targets and interacting proteins that play a role during otic development. We review our transcriptomic, yeast 2-hybrid, and proteomic approaches that have revealed a large number of new candidates. We also discuss how we have begun to identify how Six1 and co-factors interact to direct developmental events necessary for normal otic development.
MeSH term(s)	Animals ; Branchio-Oto-Renal Syndrome/genetics ; Xenopus Proteins/genetics ; Xenopus Proteins/metabolism ; Disease Models, Animal ; Homeodomain Proteins/genetics ; Xenopus laevis/genetics ; Mutation ; Xenopus/genetics
Chemical Substances	Xenopus Proteins ; Homeodomain Proteins
Language	English
Publishing date	2023-10-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2103823-5
ISSN	1552-5015 ; 0022-104X ; 1552-5007
ISSN (online)	1552-5015
ISSN	0022-104X ; 1552-5007
DOI	10.1002/jez.b.23222
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Article ; Online: Bop1 is required to establish precursor domains of craniofacial tissues.

Keer, Stephanie / Neilson, Karen M / Cousin, Helene / Majumdar, Himani D / Alfandari, Dominique / Klein, Steven L / Moody, Sally A

Genesis (New York, N.Y. : 2000)

2023 Volume 62, Issue 1, Page(s) e23580

Abstract: Bop1 can promote cell proliferation and is a component of the Pes1-Bop1-WDR12 (PeBoW) complex that regulates ribosomal RNA processing and biogenesis. In embryos, however, bop1 mRNA is highly enriched in the neural plate, cranial neural crest and placodes, ...

Abstract	Bop1 can promote cell proliferation and is a component of the Pes1-Bop1-WDR12 (PeBoW) complex that regulates ribosomal RNA processing and biogenesis. In embryos, however, bop1 mRNA is highly enriched in the neural plate, cranial neural crest and placodes, and potentially may interact with Six1, which also is expressed in these tissues. Recent work demonstrated that during development, Bop1 is required for establishing the size of the tadpole brain, retina and cranial cartilages, as well as controlling neural tissue gene expression levels. Herein, we extend this work by assessing the effects of Bop1 knockdown at neural plate and larval stages. Loss of Bop1 expanded neural plate gene expression domains (sox2, sox11, irx1) and reduced neural crest (foxd3, sox9), placode (six1, sox11, irx1, sox9) and epidermal (dlx5) expression domains. At larval stages, Bop1 knockdown reduced the expression of several otic vesicle genes (six1, pax2, irx1, sox9, dlx5, otx2, tbx1) and branchial arch genes that are required for chondrogenesis (sox9, tbx1, dlx5). The latter was not the result of impaired neural crest migration. Together these observations indicate that Bop1 is a multifunctional protein that in addition to its well-known role in ribosomal biogenesis functions during early development to establish the craniofacial precursor domains.
MeSH term(s)	Gene Expression Regulation, Developmental ; Head ; Neural Crest/metabolism ; Ribosomes/metabolism ; Skull/metabolism ; Transcription Factors/metabolism ; Xenopus laevis
Chemical Substances	Transcription Factors
Language	English
Publishing date	2023-11-16
Publishing country	United States
Document type	Letter
ZDB-ID	2004544-X
ISSN	1526-968X ; 1526-954X
ISSN (online)	1526-968X
ISSN	1526-954X
DOI	10.1002/dvg.23580
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Article ; Online: Trim-Away mediated knock down uncovers a new function for Lbh during gastrulation of Xenopus laevis.

Weir, Emma / McLinden, Gretchen / Alfandari, Dominique / Cousin, Hélène

Developmental biology

2020 Volume 470, Page(s) 74–83

Abstract: We previously identified the protein Lbh as necessary for cranial neural crest (CNC) cell migration in Xenopus through the use of morpholinos. However, Lbh is a maternally deposited protein and morpholinos achieve knockdowns through prevention of ... ...

Abstract	We previously identified the protein Lbh as necessary for cranial neural crest (CNC) cell migration in Xenopus through the use of morpholinos. However, Lbh is a maternally deposited protein and morpholinos achieve knockdowns through prevention of translation. In order to investigate the role of Lbh in earlier embryonic events, we employed the new technique "Trim-Away" to degrade this maternally deposited protein. Trim-Away utilizes the E3 ubiquitin ligase trim21 to degrade proteins targeted with an antibody and was developed in mammalian systems. Our results show that Xenopus is amenable to the Trim-Away technique. We also show that early knockdown of Lbh in Xenopus results in defects in gastrulation that present with a decrease in fibronectin matrix assembly, an increased in mesodermal cell migration and decrease in endodermal cell cohesion. We further show that the technique is also effective on a second abundant maternal protein PACSIN2. We discuss potential advantages and limit of the technique in Xenopus embryos as well as the mechanism of gastrulation inhibition.
MeSH term(s)	Adaptor Proteins, Signal Transducing/immunology ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Antibodies, Monoclonal/immunology ; Cell Movement ; Ectoderm/cytology ; Ectoderm/embryology ; Ectoderm/pathology ; Embryonic Induction ; Endoderm/cytology ; Endoderm/embryology ; Endoderm/physiology ; Fibronectins/metabolism ; Gastrulation ; Mesoderm/cytology ; Mesoderm/embryology ; Mesoderm/physiology ; Morpholinos ; Neural Crest/cytology ; Neural Crest/embryology ; Proteolysis ; Ribonucleoproteins/genetics ; Ribonucleoproteins/metabolism ; Xenopus Proteins/genetics ; Xenopus Proteins/immunology ; Xenopus Proteins/metabolism ; Xenopus Proteins/physiology ; Xenopus laevis/embryology
Chemical Substances	Adaptor Proteins, Signal Transducing ; Antibodies, Monoclonal ; Fibronectins ; Morpholinos ; PACSIN2 protein, Xenopus ; Ribonucleoproteins ; SS-A antigen ; Xenopus Proteins
Language	English
Publishing date	2020-11-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1114-9
ISSN	1095-564X ; 0012-1606
ISSN (online)	1095-564X
ISSN	0012-1606
DOI	10.1016/j.ydbio.2020.10.014
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Article ; Online: Zmym4 is required for early cranial gene expression and craniofacial cartilage formation

Karyn Jourdeuil / Karen M. Neilson / Helene Cousin / Andre L. P. Tavares / Himani D. Majumdar / Dominique Alfandari / Sally A. Moody

Frontiers in Cell and Developmental Biology, Vol

2023 Volume 11

Abstract: Introduction: The Six1 transcription factor plays important roles in the development of cranial sensory organs, and point mutations underlie craniofacial birth defects. Because Six1’s transcriptional activity can be modulated by interacting proteins, we ... ...

Abstract	Introduction: The Six1 transcription factor plays important roles in the development of cranial sensory organs, and point mutations underlie craniofacial birth defects. Because Six1’s transcriptional activity can be modulated by interacting proteins, we previously screened for candidate interactors and identified zinc-finger MYM-containing protein 4 (Zmym4) by its inclusion of a few domains with a bona fide cofactor, Sine oculis binding protein (Sobp). Although Zmym4 has been implicated in regulating early brain development and certain cancers, its role in craniofacial development has not previously been described.Methods: We used co-immunoprecipitation and luciferase-reporter assays in cultured cells to test interactions between Zmym4 and Six1. We used knock-down and overexpression of Zmym4 in embryos to test for its effects on early ectodermal gene expression, neural crest migration and craniofacial cartilage formation.Results: We found no evidence that Zmym4 physically or transcriptionally interacts with Six1 in cultured cells. Nonetheless, knockdown of endogenous Zmym4 in embryos resulted in altered early cranial gene expression, including those expressed in the neural border, neural plate, neural crest and preplacodal ectoderm. Experimentally increasing Zmym4 levels had minor effects on neural border or neural plate genes, but altered the expression of neural crest and preplacodal genes. At larval stages, genes expressed in the otic vesicle and branchial arches showed reduced expression in Zmym4 morphants. Although we did not detect defects in neural crest migration into the branchial arches, loss of Zmym4 resulted in aberrant morphology of several craniofacial cartilages.Discussion: Although Zmym4 does not appear to function as a Six1 transcriptional cofactor, it plays an important role in regulating the expression of embryonic cranial genes in tissues critical for normal craniofacial development.
Keywords	neural border ; neural plate ; preplacodal ectoderm ; neural crest ; otic vesicle ; xenopus ; Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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