scholarly journals 16p12.1 deletion orthologs are expressed in motile neural crest cells and are important for regulating craniofacial development in Xenopus laevis

2020 ◽  
Author(s):  
Micaela Lasser ◽  
Jessica Bolduc ◽  
Luke Murphy ◽  
Caroline O'Brien ◽  
Sangmook Lee ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
Neural Crest ◽  
Expression Patterns ◽  
Copy Number Variants ◽  
Neural Crest Cell ◽  
Underlying Mechanism ◽  
Craniofacial Development ◽  
Pharyngeal Arches ◽  
Individual Gene ◽  
Vertebrate Model

Copy number variants (CNVs) associated with neurodevelopmental disorders are characterized by extensive phenotypic heterogeneity. In particular, one CNV was identified in a subset of children clinically diagnosed with intellectual disabilities (ID) that results in a hemizygous deletion of multiple genes at chromosome 16p12.1. In addition to ID, individuals with this deletion display a variety of symptoms including microcephaly, seizures, cardiac defects, and growth retardation. Moreover, patients also manifest severe craniofacial abnormalities, such as micrognathia, cartilage malformation of the ears and nose, and facial asymmetries; however, the function of the genes within the 16p12.1 region have not been studied in the context of vertebrate craniofacial development. The craniofacial tissues affected in patients with this deletion all derive from the same embryonic precursor, the cranial neural crest, leading to the hypothesis that one or more of the 16p12.1 genes may be involved in regulating neural crest cell (NCC)-related processes. To examine this, we characterized the developmental role of the 16p12.1-affected gene orthologs, polr3e, mosmo, uqcrc2, and cdr2, during craniofacial morphogenesis in the vertebrate model system, Xenopus laevis. While the currently-known cellular functions of these genes are diverse, we find that they share similar expression patterns along the neural tube, pharyngeal arches, and later craniofacial structures. As these genes show co-expression in the pharyngeal arches where NCCs reside, we sought to elucidate the effect of individual gene depletion on craniofacial development and NCC migration. We find that reduction of several 16p12.1 genes significantly disrupts craniofacial and cartilage formation, pharyngeal arch migration, as well as NCC specification and motility. Thus, we have determined that some of these genes play an essential role during vertebrate craniofacial patterning by regulating specific processes during NCC development, which may be an underlying mechanism contributing to the craniofacial defects associated with the 16p12.1 deletion.

scholarly journals Wolf-Hirschhorn Syndrome-associated genes are enriched in motile neural crest and affect craniofacial development in Xenopus laevis

2018 ◽  
Author(s):  
Alexandra Mills ◽  
Elizabeth Bearce ◽  
Rachael Cella ◽  
Seung Woo Kim ◽  
Megan Selig ◽  
...  
Keyword(s):  
Cell Migration ◽  
Xenopus Laevis ◽  
Neural Crest ◽  
Developmental Disorder ◽  
Neural Crest Cell ◽  
Craniofacial Development ◽  
Cartilage Formation ◽  
Neural Crest Cell Migration ◽  
Critical Regions ◽  
Crest Cell

Wolf-Hirschhorn Syndrome (WHS) is a human developmental disorder arising from a hemizygous perturbation, typically a microdeletion, on the short arm of chromosome four. In addition to pronounced intellectual disability, seizures, and delayed growth, WHS presents with a characteristic facial dysmorphism and varying prevalence of microcephaly, micrognathia, cartilage malformation in the ear and nose, and facial asymmetries. These affected craniofacial tissues all derive from a shared embryonic precursor, the cranial neural crest, inviting the hypothesis that one or more WHS-affected genes may be critical regulators of neural crest development or migration. To explore this, we characterized expression of multiple genes within or immediately proximal to defined WHS critical regions, across the span of craniofacial development in the vertebrate model system Xenopus laevis. This subset of genes, WHSC1, WHSC2, LETM1, and TACC3, are diverse in their currently-elucidated cellular functions; yet we find that their expression demonstrates shared tissue-specific enrichment within the anterior neural tube, pharyngeal arches, and later craniofacial structures. We examine the ramifications of this by characterizing craniofacial development and neural crest migration following individual gene depletion. We observe that several WHS-associated genes significantly impact facial patterning, cartilage formation, pharyngeal arch migration, and neural crest motility, and can separately contribute to forebrain scaling. Thus, we have determined that numerous genes within and surrounding the defined WHS critical regions potently impact craniofacial patterning, suggesting their role in WHS presentation may stem from essential functions during neural crest-derived tissue formation.Author SummaryWolf-Hirschhorn Syndrome (WHS), a developmental disorder caused by small deletions on chromosome four, manifests with pronounced and characteristic facial malformation. While genetic profiling and case studies provide insights into how broader regions of the genome affect the syndrome’s severity, we lack a key component of understanding its pathology; a basic knowledge of how individual WHS-affected genes function during development. Importantly, many tissues affected by WHS derive from shared embryonic origin, the cranial neural crest. This led us to hypothesize that genes deleted in WHS may hold especially critical roles in this tissue. To this end, we investigated the roles of four WHS-associated genes during neural crest cell migration and facial patterning. We show that during normal development, expression of these genes is enriched in migratory neural crest and craniofacial structures. Subsequently, we examine their functional roles during facial patterning, cartilage formation, and forebrain development, and find that their depletion recapitulates features of WHS craniofacial malformation. Additionally, two of these genes directly affect neural crest cell migration rate. We report that depletion of WHS-associated genes is a potent effector of neural crest-derived tissues, and suggest that this explains why WHS clinical presentation shares so many characteristics with classic neurochristopathies.

scholarly journals Wolf-Hirschhorn Syndrome-Associated Genes Are Enriched in Motile Neural Crest Cells and Affect Craniofacial Development in Xenopus laevis

2019 ◽  
Vol 10 ◽  
Author(s):  
Alexandra Mills ◽  
Elizabeth Bearce ◽  
Rachael Cella ◽  
Seung Woo Kim ◽  
Megan Selig ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
Neural Crest ◽  
Neural Crest Cells ◽  
Craniofacial Development

scholarly journals Vgll2a is required for neural crest cell survival during zebrafish craniofacial development

2011 ◽  
Vol 357 (1) ◽  
pp. 269-281 ◽  
Author(s):  
Christopher W. Johnson ◽  
Laura Hernandez-Lagunas ◽  
Weiguo Feng ◽  
Vida Senkus Melvin ◽  
Trevor Williams ◽  
...  
Keyword(s):  
Neural Crest ◽  
Cell Survival ◽  
Neural Crest Cell ◽  
Craniofacial Development ◽  
Crest Cell

sucker encodes a zebrafish Endothelin-1 required for ventral pharyngeal arch development

Development ◽  
2000 ◽  
Vol 127 (17) ◽  
pp. 3815-3828 ◽  
Author(s):  
C.T. Miller ◽  
T.F. Schilling ◽  
K. Lee ◽  
J. Parker ◽  
C.B. Kimmel
Keyword(s):  
Neural Crest ◽  
Expression Patterns ◽  
Neural Crest Cells ◽  
Paraxial Mesoderm ◽  
Dorsoventral Patterning ◽  
Surface Ectoderm ◽  
Pharyngeal Arches ◽  
Endothelin 1 ◽  
Lower Jaw ◽  
Arch Neural

Mutation of sucker (suc) disrupts development of the lower jaw and other ventral cartilages in pharyngeal segments of the zebrafish head. Our sequencing, cosegregation and rescue results indicate that suc encodes an Endothelin-1 (Et-1). Like mouse and chick Et-1, suc/et-1 is expressed in a central core of arch paraxial mesoderm and in arch epithelia, both surface ectoderm and pharyngeal endoderm, but not in skeletogenic neural crest. Long before chondrogenesis, suc/et-1 mutant embryos have severe defects in ventral arch neural crest expression of dHAND, dlx2, msxE, gsc, dlx3 and EphA3 in the anterior arches. Dorsal expression patterns are unaffected. Later in development, suc/et-1 mutant embryos display defects in mesodermal and endodermal tissues of the pharynx. Ventral premyogenic condensations fail to express myoD, which correlates with a ventral muscle defect. Further, expression of shh in endoderm of the first pharyngeal pouch fails to extend as far laterally as in wild types. We use mosaic analyses to show that suc/et-1 functions nonautonomously in neural crest cells, and is thus required in the environment of postmigratory neural crest cells to specify ventral arch fates. Our mosaic analyses further show that suc/et-1 nonautonomously functions in mesendoderm for ventral arch muscle formation. Collectively our results support a model for dorsoventral patterning of the gnathostome pharyngeal arches in which Et-1 in the environment of the postmigratory cranial neural crest specifies the lower jaw and other ventral arch fates.

scholarly journals Vgl-2a is Required for Neural Crest Cell Survival During Zebrafish Craniofacial Development

2010 ◽  
Vol 344 (1) ◽  
pp. 447
Author(s):  
Christopher W. Johnson ◽  
Weiguo Feng ◽  
Trevor Williams ◽  
Kristin Artinger
Keyword(s):  
Neural Crest ◽  
Cell Survival ◽  
Neural Crest Cell ◽  
Craniofacial Development ◽  
Crest Cell

scholarly journals Williams Syndrome Transcription Factor is critical for neural crest cell function in Xenopus laevis

2012 ◽  
Vol 129 (9-12) ◽  
pp. 324-338 ◽  
Author(s):  
Chris Barnett ◽  
Oya Yazgan ◽  
Hui-Ching Kuo ◽  
Sreepurna Malakar ◽  
Trevor Thomas ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Xenopus Laevis ◽  
Neural Crest ◽  
Williams Syndrome ◽  
Cell Function ◽  
Neural Crest Cell ◽  
Crest Cell

scholarly journals Crispld2 is required for neural crest cell migration and cell viability during zebrafish craniofacial development

genesis ◽  
2015 ◽  
Vol 53 (10) ◽  
pp. 660-667 ◽  
Author(s):  
Eric C. Swindell ◽  
Qiuping Yuan ◽  
Lorena E. Maili ◽  
Bhavna Tandon ◽  
Daniel S. Wagner ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Viability ◽  
Neural Crest ◽  
Neural Crest Cell ◽  
Craniofacial Development ◽  
Neural Crest Cell Migration ◽  
Crest Cell

scholarly journals The ubiquitin ligase Nedd4 regulates craniofacial development by promoting cranial neural crest cell survival and stem-cell like properties

2013 ◽  
Vol 383 (2) ◽  
pp. 186-200 ◽  
Author(s):  
Sophie Wiszniak ◽  
Samuela Kabbara ◽  
Rachael Lumb ◽  
Michaela Scherer ◽  
Genevieve Secker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neural Crest ◽  
Cell Survival ◽  
Ubiquitin Ligase ◽  
Neural Crest Cell ◽  
Craniofacial Development ◽  
Cranial Neural Crest ◽  
Cranial Neural Crest Cell ◽  
Crest Cell

scholarly journals Serotonin is required for pharyngeal arch morphogenesis in zebrafish

2014 ◽  
Author(s):  
Katarina Kotnik Halavaty ◽  
Michael Bader ◽  
Saleh Bashammakh ◽  
Salim Seyfried
Keyword(s):  
Neural Crest ◽  
Tryptophan Hydroxylase ◽  
Expression Patterns ◽  
Pharyngeal Arch ◽  
Pharyngeal Arches ◽  
Early Markers ◽  
Morpholino Oligonucleotides ◽  
Antisense Morpholino Oligonucleotides ◽  
Induced Defects

Serotonin (5-HT) is not only a neurotransmitter but also a mediator of developmental processes in vertebrates. In this study, we analyzed the importance of 5-HT during zebrafish development. The expression patterns of three zebrafish tryptophan hydroxylase isoforms (Tph1A, Tph1B, Tph2), the rate-limiting enzymes in 5-HT synthesis, were analyzed and compared to the appearance and distribution of 5-HT. 5-HT was found in the raphe nuclei correlating with tph2 expression and in the pineal gland correlating with tph1a and tph2 expression. tph2 deficient fish generated with antisense morpholino oligonucleotides exhibited morphogenesis defects during pharyngeal arch development. The correct specification of neural crest cells was not affected in tph2 morphants as shown by the expression of early markers, but the survival and differentiation of pharyngeal arch progenitor cells were impaired. An organizing role of 5-HT in pharyngeal arch morphogenesis was suggested by a highly regular pattern of 5-HT positive cells in this tissue. Moreover, the 5-HT2B receptor was expressed in the pharyngeal arches and its pharmacological inhibition also induced defects in pharyngeal arch morphogenesis. These results support an important role of Tph2-derived serotonin as a morphogenetic factor in the development of neural crest derived tissues.

scholarly journals Vital dye labelling of Xenopus laevis trunk neural crest reveals multipotency and novel pathways of migration

Development ◽  
1993 ◽  
Vol 118 (2) ◽  
pp. 363-376 ◽  
Author(s):  
A. Collazo ◽  
M. Bronner-Fraser ◽  
S.E. Fraser
Keyword(s):  
Xenopus Laevis ◽  
Neural Crest ◽  
Neural Tube ◽  
Single Cells ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Pigment Cells ◽  
Spinal Ganglia ◽  
Posterior Portion ◽  
Precise Position

Although the Xenopus embryo has served as an important model system for both molecular and cellular studies of vertebrate development, comparatively little is known about its neural crest. Here, we take advantage of the ease of manipulation and relative transparency of Xenopus laevis embryos to follow neural crest cell migration and differentiation in living embryos. We use two techniques to study the lineage and migratory patterns of frog neural crest cells: (1) injections of DiI or lysinated rhodamine dextran (LRD) into small populations of neural crest cells to follow movement and (2) injections of LRD into single cells to follow cell lineage. By using non-invasive approaches that allow observations in living embryos and control of the time and position of labelling, we have been able to expand upon the results of previous grafting experiments. Migration and differentiation of the labelled cells were observed over time in individual living embryos, and later in sections to determine precise position and morphology. Derivatives populated by the neural crest are the fins, pigment stripes, spinal ganglia, adrenal medulla, pronephric duct, enteric nuclei and the posterior portion of the dorsal aorta. In the rostral to mid-trunk levels, most neural crest cells migrate along two paths: a dorsal pathway into the fin, followed by presumptive fin cells, and a ventral pathway along the neural tube and notochord, followed by presumptive pigment, sensory ganglion, sympathetic ganglion and adrenal medullary cells. In the caudal trunk, two additional paths were noted. One group of cells moves circumferentially within the fin, in an arc from dorsal to ventral; another progresses ventrally to the anus and subsequently populates the ventral fin. By labelling individual precursor cells, we find that neural tube and neural crest cells often share a common precursor. The majority of clones contain labelled progeny cells in the dorsal fin. The remainder have progeny in multiple derivatives including spinal ganglion cells, pigment cells, enteric cells, fin cells and/or neural tube cells in all combinations, suggesting that many premigratory Xenopus neural crest precursors are multipotent.

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