The Hedgehog Co-Receptor BOC Differentially Regulates SHH Signaling During Craniofacial Development

Echevarría-Andino, Martha L.; Allen, Benjamin L.

doi:10.1101/2020.02.04.934497

Cited by 6 publications

(1 citation statement)

References 61 publications

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“…Thus, from a developmental (and indeed clinical) perspective, constraints that limit the amount of permissible variation during early developmental stages are essential. For example, the craniofacial skeleton arises within the vertebrate embryo through a highly conserved set of molecular and cellular events 16‐26 . Variation in these processes is generally low, and likely selected against, as they can lead to maladaptive and lethal phenotypes 17,19,27‐36 .…”

Section: Introductionmentioning

confidence: 99%

Zebrafishcrocc2mutants exhibit divergent craniofacial shape, misregulated variability, and aberrant cartilage morphogenesis

Packard

Gilbert

Tetrault

et al. 2023

Developmental Dynamics

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Background Phenotypic variation is of paramount importance in development, evolution, and human health; however, the molecular mechanisms that influence organ shape and shape variability are not well understood. During craniofacial development, the behavior of skeletal precursors is regulated by both biochemical and environmental inputs, and the primary cilia play critical roles in transducing both types of signals. Here, we examine a gene that encodes a key constituent of the ciliary rootlets, crocc2, and its role in cartilage morphogenesis in larval zebrafish. Results Geometric morphometric analysis of crocc2 mutants revealed altered craniofacial shapes and expanded variation. At the cellular level, we observed altered chondrocyte shapes and planar cell polarity across multiple stages in crocc2 mutants. Notably, cellular defects were specific to areas that experience direct mechanical input. Cartilage cell number, apoptosis, and bone patterning were not affected in crocc2 mutants. Conclusions Whereas “regulatory” genes are widely implicated in patterning the craniofacial skeleton, genes that encode “structural” aspects of the cell are increasingly implicated in shaping the face. Our results add crocc2 to this list, and demonstrate that it affects craniofacial geometry and canalizes phenotypic variation. We propose that it does so via mechanosensing, possibly through the ciliary rootlet. If true, this would implicate a new organelle in skeletal development and evolution.

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Section: Introductionmentioning

confidence: 99%

Zebrafishcrocc2mutants exhibit divergent craniofacial shape, misregulated variability, and aberrant cartilage morphogenesis

Packard

Gilbert

Tetrault

et al. 2023

Developmental Dynamics

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Differential regulation of SHH signaling and the developmental control of species-specific jaw size through neural crest-mediated Gas1 expression

Vavrušová

Chu

Nguyen

et al. 2021

Preprint

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Developmental control of jaw size is crucial to prevent disease and facilitate evolution. We have shown that species-specific differences in jaw size are established by neural crest mesenchyme (NCM), which are the jaw progenitors that migrate into the mandibular primordia. NCM relies on multiple signaling molecules including Sonic Hedgehog (SHH) to mediate interactions with mandibular epithelium that facilitate outgrowth of the jaws. SHH signaling is known to promote outgrowth and so we tested if differential regulation of the SHH pathway can account for species-specific variation in mandibular primordia size. We analyze gene expression of SHH pathway members in duck, chick, and quail, and find higher transcriptional activation in the larger mandibular primordia of duck relative to those of chick and quail. We generate quail-duck chimeras and demonstrate that such activation is NCM-mediated. Gain- and loss-of-function experiments reveal a species-specific response to SHH signaling, with the target Gas1 being most sensitive to manipulations. Gas1 overexpression and knockdown in NCM alters cell number and/or mandibular primordia size. Our work suggests that NCM-mediated changes in SHH signaling may modulate jaw size during development, disease, and evolution.

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cdonandbocaffect trunk neural crest cell migration non-cell autonomously through a reduction of hedgehog signaling in zebrafish slow-twitch muscle

Lencer

Prekeris

Artinger³

2022

Preprint

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The immunoglobin superfamily members cdon and boc are transmembrane proteins implicated in regulating hedgehog signaling during vertebrate development. Recent work showing roles for these genes in axon guidance and neural crest cell migration further suggest that cdon/boc may play additional functions in regulating directed cell movements during development. Here we use novel and existing mutants to investigate a role for cdon and boc in zebrafish neural crest cell migration. We find that single cdon or boc mutant embryos exhibit normal neural crest phenotypes, but that neural crest migration is strikingly disrupted in double cdon/boc mutant embryos. We further show that this neural crest migration phenotype is associated with defects to the differentiation of slow-twitch muscle cells, and that this slow-twitch muscle phenotype is a consequence of reduced hedgehog signaling in mutant fish. While neural crest migratory ability is not affected in double mutant embryos, neural crest directionality is severely affected. These data suggest that neural crest migration defects are likely to be secondary to defects in slow-twitch muscle differentiation. Combined, our data add to a growing literature showing that cdon and boc act synergistically to promote hedgehog signaling during vertebrate development, and provide a foundation for using zebrafish to further study the function of these hedgehog receptor paralogs.

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The Hedgehog Co-Receptor BOC Differentially Regulates SHH Signaling During Craniofacial Development

Cited by 6 publications

References 61 publications

Zebrafishcrocc2mutants exhibit divergent craniofacial shape, misregulated variability, and aberrant cartilage morphogenesis

Zebrafishcrocc2mutants exhibit divergent craniofacial shape, misregulated variability, and aberrant cartilage morphogenesis

Differential regulation of SHH signaling and the developmental control of species-specific jaw size through neural crest-mediated Gas1 expression

cdonandbocaffect trunk neural crest cell migration non-cell autonomously through a reduction of hedgehog signaling in zebrafish slow-twitch muscle

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