Cadherin‐7 mediates proper neural crest cell–placodal neuron interactions during trigeminal ganglion assembly

Abstract

Summary The cranial trigeminal ganglia play a vital role in the peripheral nervous system through their relay of sensory information from the vertebrate head to the brain. These ganglia are generated from the intermixing and coalescence of two distinct cell populations: cranial neural crest cells and placodal neurons. Trigeminal ganglion assembly requires the formation of cadherin-based adherens junctions within the neural crest cell and placodal neuron populations; however, the molecular composition of these adherens junctions is still unknown. Herein, we aimed to define the spatio-temporal expression pattern and function of Cadherin-7 during early chick trigeminal ganglion formation. Our data reveal that Cadherin-7 is expressed exclusively in migratory cranial neural crest cells and is absent from trigeminal neurons. Using molecular perturbation experiments, we demonstrate that modulation of Cadherin-7 in neural crest cells influences trigeminal ganglion assembly, including the organization of neural crest cells and placodal neurons within the ganglionic anlage. Moreover, alterations in Cadherin-7 levels lead to changes in the morphology of trigeminal neurons. Taken together, these findings provide additional insight into the role of cadherin-based adhesion in trigeminal ganglion formation, and, more broadly, the molecular mechanisms that orchestrate the cellular interactions essential for cranial gangliogenesis.

Selective disruption of trigeminal sensory neurogenesis and differentiation in a mouse model of 22q11.2 deletion syndrome

“…Thus, we re-analyzed the expression of genes and splice isoforms involved in cell-cell adhesion and signaling using a previously generated RNA-seq dataset of E10.5 wild-type and LgDel CNgV transcriptomes from five biological replicates of pooled ganglia from multiple embryos and litters ( Maynard et al, 2020a ). We defined several sets of cell adhesion or cell-cell interaction genes: Notch and related factors ( Siebel and Lendahl, 2017 ); Connexin ( Gja ) gap junction subunits ( Swayne and Bennett, 2016 ); Cxcl ligands and the Cxcr4 receptor ( Kawaguchi et al, 2019 ); Wnt ligands/receptors ( Steinhart and Angers, 2018 ); and cadherin (Cdh)/catenin (Ctn) mediators ( Brault et al, 2001 ; Shiau and Bronner-Fraser, 2009 ; Wu and Taneyhill, 2019 ). Consistent with our expression level analysis for all wild-type versus LgDel CNgV transcripts ( Maynard et al, 2020a ), 22/22 Notch-related, 10/12 Gja, and 3/4 Cxcl/Cxcr genes had higher coefficients of variation (CVs) in LgDel versus wild-type CNgV; however, none were differentially expressed ( …”

“…Thus, neural crest migration and coalescence into CNgV may be altered. In addition, local signaling between neural crest-derived sensory ganglion cells ( Wakamatsu, 2011 ; Wakamatsu et al, 2000 ) or placode- versus neural crest-derived cells ( Shiau and Bronner-Fraser, 2009 ; Shiau et al, 2008 ; Steventon et al, 2014 ; Wu and Taneyhill, 2019 ) may be disrupted due to divergent specification of distinct CNgV precursors. These changes, presumably due to diminished 22q11 gene dosage in the hindbrain or in CNgV cells themselves ( Karpinski et al, 2014 ; Maynard et al, 2003 , 2020a ; Meechan et al, 2006 ), could compromise subsequent axon growth, target innervation or functional differentiation leading to aberrant transduction, relay or transmission of orofacial sensory information and subsequent oropharyngeal dysfunction, including pediatric dysphagia.…”

Evolutionary and Developmental Associations of Neural Crest and Placodes in the Vertebrate Head: Insights From Jawless Vertebrates

“…A similar role has also been described in jawed vertebrates in which neural crest cells form "corridors" that guide and physically shape placode-derived sensory neurons in the head (Freter et al, 2013). The molecular mechanisms of these types of interactions in jawed vertebrates seem to involve intercellular signaling pathways and adhesion proteins (Shiau et al, 2008;Wu et al, 2014;Shah and Taneyhill, 2015;Wu and Taneyhill, 2019), which have been shown recently to influence the patterning of cranial ganglia in lampreys (York et al, 2018).…”

Stable integration of an optimized inducible promoter system enables spatiotemporal control of gene expression throughout avian development

“…Electroporation is a very effective technique for introducing expression constructs into the premigratory cephalic NCM particularly by targeting the neural folds in stage HH8.5 embryos ( Creuzet et al, 2002 ; Krull, 2004 ; McLennan and Kulesa, 2007 ; Hall et al, 2014 ). Several DNA constructs containing a robust chicken β-actin promoter, a CMV promoter, an internal ribosome entry site (IRES), and a bicistronic reporter with green fluorescent protein (GFP) have been widely adopted including pMES, pCIG, and pCAβ ( Swartz et al, 2001 ; Megason and McMahon, 2002 ; McLarren et al, 2003 ; Sauka-Spengler and Barembaum, 2008 ; Jhingory et al, 2010 ; Hall et al, 2014 ; Yang et al, 2014 ; Gammill et al, 2019 ; Wu and Taneyhill, 2019 ). Electroporation can also efficiently enable gene repression using RNA interference (RNAi) and antisense morpholino oligonucleotides ( Tucker, 2001 ; Kos et al, 2003 ; Chesnutt and Niswander, 2004 ; Krull, 2004 ; Nakamura et al, 2004 ; Rao et al, 2004 ; Das et al, 2006 ; Sauka-Spengler and Barembaum, 2008 ; Gammill et al, 2019 ).…”