Ellis Van Creveld2 is Required for Postnatal Craniofacial Bone Development

Badri, Mohammed K.; Zhang, Honghao; Ohyama, Yoshio; Venkitapathi, Sundharamani; Kamiya, Nobuhiro; Takeda, Hitoshi; Ray, Manas K.; Scott, Greig; Tsuji, Takehito; Kunieda, Tetsuo; Mishina, Yuji; Mochida, Yoshiyuki

doi:10.1002/ar.23353

Cited by 9 publications

(18 citation statements)

References 26 publications

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“…In the current studies, we identified that the skull length, nasal bone length, frontal bone length, incisor length, and total cranial base length are all significantly smaller in Evc2 m mutants than in controls at postnatal day 8. These observations are consistent with previous reports using different methods to study abnormal craniofacial development (Badri et al, ) and abnormal tooth development (Zhang et al, ). Our previous studies demonstrated that Evc2 is expressed in nearly all tissues in the skull (Badri et al, ).…”

Section: Discussionsupporting

confidence: 93%

“…At postnatal day 8, Evc2 m exhibited smaller skull size compared to the control group. The gross morphology demonstrated in the Evc2 mutant mice is similar both to phenotypes of Evc mutant mice (Ruiz‐Perez et al, ; Pacheco et al, ; Badri et al, ) and to symptoms observed in EvC patients (Ellis and van Creveld, ; McKusick et al, ). These facts suggest that the molecular pathological mechanism leading to craniofacial abnormalities in Evc2 mutant mice is the same as those in Evc mutant mice and in EvC patients.…”

Section: Discussionsupporting

confidence: 68%

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The Role of Ellis‐Van Creveld 2(EVC2) in Mice During Cranial Bone Development

Kwon

Louie

Kulkarni

et al. 2017

The Anatomical Record

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EvC syndrome is a type of autosomal-recessive chondrodysplasia. Previous case studies in patients suggest abnormal craniofacial development, in addition to dwarfism and tooth abnormalities. To investigate how craniofacial development is affected in EvC patients, surface models were generated from micro-CT scans of control mice, Evc2 global mutant mice and Evc2 neural crest-specific mutant mice. The anatomic landmarks were placed on the surface model to assess the morphological abnormalities in the Evc2 mutants. Through analyzing the linear and angular measurements between landmarks, we identified a smaller overall skull, shorter nasal bone, shorter frontal bone, and shorter cranial base in the Evc2 global mutants. By comparing neural crest-specific Evc2 mutants with control mice, we demonstrated that the abnormalities within the mid-facial regions are not accounted for by the Evc2 mutation within these regions. Additionally, we also identified disproportionate length to width ratios in the Evc2 mutants at all levels from anterior to posterior of the skull. Overall, this study demonstrates a more comprehensive analysis on the craniofacial morphological abnormalities in EvC syndrome and provides the developmental insight to appreciate the impact of Evc2 mutation within the neural crest cells on multiple aspects of skull deformities. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:46-55, 2018. © 2017 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 68%

The Role of Ellis‐Van Creveld 2(EVC2) in Mice During Cranial Bone Development

Kwon

Louie

Kulkarni

et al. 2017

The Anatomical Record

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“…Radiograph-based cephalometry used in murine skulls is very similar to that used in human, which has practical and successful clinical applications. Although it was reported that certain landmarks are difficult to identify on two-dimensional radiograph of mouse skull (Bloom et al, 2006 ), radiograph-based cephalometry has been used successfully to identify morphometric changes in transgenic mice (Chung et al, 1997 ; McAlarney et al, 2001 ; Yagasaki et al, 2003 ; Simon et al, 2014 ; Badri et al, 2016 ). Thus, radiograph-based cephalometric analysis is an alternative to μCT-based craniofacial morphological measurement when the landmarks can be clearly identified.…”

Section: Discussionmentioning

confidence: 99%

Postnatal Craniofacial Skeletal Development of Female C57BL/6NCrl Mice

et al. 2017

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The craniofacial skeleton is a complex and unique structure. The perturbation of its development can lead to craniofacial dysmorphology and associated morbidities. Our ability to prevent or mitigate craniofacial skeletal anomalies is at least partly dependent on our understanding of the unique physiological development of the craniofacial skeleton. Mouse models are critical tools for the study of craniofacial developmental abnormalities. However, there is a lack of detailed normative data of mouse craniofacial skeletal development in the literature. In this report, we employed high-resolution micro-computed tomography (μCT) in combination with morphometric measurements to analyze the postnatal craniofacial skeletal development from day 7 (P7) through day 390 (P390) of female C57BL/6NCrl mice, a widely used mouse strain. Our data demonstrates a unique craniofacial skeletal development pattern in female C57BL/6NCrl mice, and differentiates the early vs. late craniofacial growth patterns. Additionally, our data documents the complex and differential changes in bone parameters (thickness, bone volume, bone volume/tissue volume, bone mineral density, and tissue mineral density) of various craniofacial bones with different embryonic origins and ossification mechanisms during postnatal growth, which underscores the complexity of craniofacial bone development and provides a reference standard for future quantitative analysis of craniofacial bones.

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“…Generating our own Evc2 mutant mice enabled us to characterize the pathological mechanisms leading to abnormal appendicular bone and hypomorphic enamel development ( Zhang et al, 2015 , 2016a , b ). Our subsequent studies further demonstrated the expression of Evc2 in the mid-facial regions ( Badri et al, 2016a ) and mid-facial defects in Evc2 global mutant mice ( Badri et al, 2016b ). We most recently employed a conditional, Cre -mediated approach toward deleting Evc2 in a neural crest-specific manner.…”

Section: Introductionmentioning

confidence: 74%

“…Our previous studies indicated that global Evc2 mutation led to retarded growth and significantly affected both body and head size ( Zhang et al, 2015 ; Badri et al, 2016b ). To better characterize the function of Evc2 in craniofacial development, we generated mutant mice with Evc2 deleted in the neural crest-derived cells.…”

Section: Resultsmentioning

confidence: 99%

A Ciliary Protein EVC2/LIMBIN Plays a Critical Role in the Skull Base for Mid-Facial Development

et al. 2018

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Ellis-van Creveld (EvC) syndrome is an autosomal recessive chondrodysplastic disorder. Affected patients present a wide spectrum of symptoms including short stature, postaxial polydactyly, and dental abnormalities. We previously disrupted Evc2, one of the causative genes for EvC syndrome, in mice using a neural crest-specific, Cre-mediated approach (i.e., P0-Cre, referred to as Evc2 P0 mutants). Despite the fact that P0-Cre predominantly targets the mid-facial region, we reported that many mid-facial defects identified in Evc2 global mutants are not present in Evc2 P0 mutants at postnatal day 8 (P8). In the current study, we used multiple Cre lines (P0-Cre and Wnt1-Cre, respectively), to specifically delete Evc2 in neural crest-derived tissues and compared the resulting mid-facial defects at multiple time points (P8 and P28, respectively). While both Cre lines indistinguishably targeted the mid-facial region, they differentially targeted the anterior portion of the skull base. By comprehensively analyzing the shapes of conditional mutant skulls, we detected differentially affected mid-facial defects in Evc2 P0 mutants and Evc2 Wnt1 mutants. Micro-CT analysis of the skull base further revealed that the Evc2 mutation leads to a differentially affected skull base, caused by premature closure of the intersphenoid synchondrosis (presphenoidal synchondrosis), which limited the elongation of the anterior skull base during the postnatal development of the skull. Given the importance of the skull base in mid-facial bone development, our results suggest that loss of function of Evc2 within the skull base secondarily leads to many aspects of the mid-facial defects developed by the EvC syndrome.

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Ellis Van Creveld2 is Required for Postnatal Craniofacial Bone Development

Cited by 9 publications

References 26 publications

The Role of Ellis‐Van Creveld 2(EVC2) in Mice During Cranial Bone Development

The Role of Ellis‐Van Creveld 2(EVC2) in Mice During Cranial Bone Development

Postnatal Craniofacial Skeletal Development of Female C57BL/6NCrl Mice

A Ciliary Protein EVC2/LIMBIN Plays a Critical Role in the Skull Base for Mid-Facial Development

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