Transcriptional dysregulation in developing trigeminal sensory neurons in the LgDel mouse model of DiGeorge 22q11.2 deletion syndrome

Maynard, Thomas M.; Horvath, Anélia; Bernot, James P.; Karpinski, Beverly A.; Tavares, Andre L.P.; Shah, Ankita; Qin, Zheng; Olender, Jacqueline; Moody, Sally A.; Fraser, Claire M.; LaMantia, Anthony S.; Lee, Norman H.

doi:10.1093/hmg/ddaa067

Cited by 6 publications

(15 citation statements)

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“…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 WT versus LgDel CNgV transcripts(Maynard et al, 2020a), 22/22 Notch-related, 10/12 Gja, and 3/4 Cxcl/Cxcr genesDisease Models & Mechanisms • DMM • Accepted manuscript had higher coefficients of variation (CVs) in LgDel versus WT CNgV; however, none are differentially expressed (Supp. Figure 1A).…”

supporting

confidence: 83%

“…Thus, we determined relative frequencies of Six1+, Wnt1 Cre +, Six1+/Wnt1 Cre +, and Six1-/Wnt1 Cre -/DAPI+ only cells ("DAPI+") in WT versus LgDel E9.5 CNgV (Figure 2A). The "DAPI+ only" cells represent a subset of Foxd3+/Six1-presumably neural crest cells not included in the Wnt1 Cre transcriptional lineage Maynard et al, 2020a); we refer to them as "DAPI+" for convenience. At E9.5, there is no significant LgDel, n=9 ganglia, 7 embryos, 4 litters; WT, n=7 ganglia, 4 embryos, 3 litters); however, the proportion of LgDel Six1+/Wnt1 Cre + cells increases significantly (p=0.0009, t-test) and that of DAPI+ cells decreases significantly (p=0.02, t-test).…”

Section: Divergence Of Progenitor Classes In Lgdel Cngvmentioning

confidence: 99%

“…To further define cellular diversity in P8 LgDel and WT CNgV, we compared relationships between Wnt1 Cre + sensory neurons at P8 with markers of nociceptor identity: TrkA ( Figure 7J,K) and TrpV1 (Figure 7L,M) WT versus LgDel individuals requires adequate sampling and quantification to identify distinctions (Maynard et al, 2008;Meechan et al, 2007;Meechan et al, 2015a;Meechan et al, 2006;Meechan et al, 2009;Motahari et al, 2019). It is likely that additional phenotypes in a broad range of neurodevelopmental disorders-especially those associated with copy number variants or polymorphic alleles-reflect similarly subtle, variable changes of early development that have, as yet, escaped detection.…”

Section: Disease Models and Mechanisms • Dmm • Accepted Manuscriptmentioning

confidence: 99%

“…Neural crest-derived CNgV cells in LgDel embryos may be particularly vulnerable to altered differentiation. They arise from anterior hindbrain regions (rhombomeres 2 and 3) that are anomalously patterned to a more posterior identity ( Karpinski et al, 2014 ; Maynard et al, 2020a ). Thus, neural crest migration and coalescence into CNgV may be altered.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Karpinski

Maynard

Bryan

et al. 2021

Disease Models &Amp; Mechanisms

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22q11.2 Deletion Syndrome (22q11DS) is a neurodevelopmental disorder associated with cranial nerve anomalies and disordered oropharyngeal function including pediatric dysphagia. Using the LgDel 22q11DS mouse model, we asked whether sensory neuron differentiation in the trigeminal ganglion (CNgV) , which is essential for normal orofacial function, is disrupted. We did not detect changes in cranial placode cell translocation or neural crest migration at early stages of LgDel CNgV development. As the ganglion coalesces, however, proportions of placode-derived LgDel CNgV cells increase relative to neural crest cells. In addition, local aggregation of placode-derived cells increases and aggregation of neural crest-derived cells decreases in LgDel CNgV. This change in cell-cell relationships was accompanied by altered proliferation of placode-derived cells at E9.5, and premature neurogenesis from neural crest-derived precursors, reflected by increased frequency of asymmetric neurogenic divisions for neural crest-derived precursors by E10.5. These early differences in LgDel CNgV genesis prefigure changes in sensory neuron differentiation and gene expression by P8, when early signs of cranial nerve dysfunction associated with pediatric dysphagia are observed in LgDel mice. Apparently, 22q11 deletion destabilizes CNgV sensory neuron genesis and differentiation by increasing variability in cell-cell interaction, proliferation, and sensory neuron differentiation. This early developmental divergence and its consequences may contribute to oropharyngeal dysfunction including suckling, feeding and swallowing disruptions at birth and additional orofacial sensory/motor deficits throughout life.

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supporting

confidence: 83%

Section: Divergence Of Progenitor Classes In Lgdel Cngvmentioning

confidence: 99%

Section: Disease Models and Mechanisms • Dmm • Accepted Manuscriptmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Karpinski

Maynard

Bryan

et al. 2021

Disease Models &Amp; Mechanisms

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Advances in Swallowing Neurophysiology Across Pediatric Development: Current Evidence and Insights

Malandraki

Arkenberg

2021

Curr Phys Med Rehabil Rep

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Purpose of Review This review article analyzes current evidence on the neurophysiology of swallowing during development and offers expert opinion on clinical implications and future research directions. Recent Findings In the past 5 years, basic and clinical research has offered advances in our understanding of pediatric swallowing neurophysiology. Animal models have elucidated the role of brainstem circuits and the peripheral and central nervous systems in neonatal swallowing. Recent human studies have further showcased that fetal and infant swallowing require cerebral inputs in order to develop functionally. Finally, neurophysiological and neuroimaging studies are starting to better define these cerebral inputs, as well as neuroplastic adaptations that may be needed for optimal feeding development.Summary The neural development of swallowing is a complex and dynamic process. Continued research is needed to better understand influences on swallowing neural development, which can be essential for improving prevention, diagnosis, and interventions for pediatric dysphagia.

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Polygenicity in a box: Copy number variants, neural circuit development, and neurodevelopmental disorders

LaMantia

2024

Current Opinion in Neurobiology

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Transcriptional dysregulation in developing trigeminal sensory neurons in the LgDel mouse model of DiGeorge 22q11.2 deletion syndrome

Cited by 6 publications

References 0 publications

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

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

Advances in Swallowing Neurophysiology Across Pediatric Development: Current Evidence and Insights

Polygenicity in a box: Copy number variants, neural circuit development, and neurodevelopmental disorders

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