A Ciliary Protein EVC2/LIMBIN Plays a Critical Role in the Skull Base for Mid-Facial Development
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 us...
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2018.01484/full |
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| author | Anshul K. Kulkarni Ke’ale W. Louie Marilia Yatabe Antonio Carlos de Oliveira Ruellas Yoshiyuki Mochida Lucia H. S. Cevidanes Yuji Mishina Honghao Zhang |
| author_facet | Anshul K. Kulkarni Ke’ale W. Louie Marilia Yatabe Antonio Carlos de Oliveira Ruellas Yoshiyuki Mochida Lucia H. S. Cevidanes Yuji Mishina Honghao Zhang |
| author_sort | Anshul K. Kulkarni |
| collection | DOAJ |
| description | 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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| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-20T17:41:41Z |
| publishDate | 2018-10-01 |
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| series | Frontiers in Physiology |
| spelling | doaj.art-e823789df5b045a3a5eb115abe05c4fc2022-12-21T19:31:06ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-10-01910.3389/fphys.2018.01484398983A Ciliary Protein EVC2/LIMBIN Plays a Critical Role in the Skull Base for Mid-Facial DevelopmentAnshul K. Kulkarni0Ke’ale W. Louie1Marilia Yatabe2Antonio Carlos de Oliveira Ruellas3Yoshiyuki Mochida4Lucia H. S. Cevidanes5Yuji Mishina6Honghao Zhang7Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, United StatesDepartment of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, United StatesDepartment of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI, United StatesDepartment of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI, United StatesDepartment of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, MA, United StatesDepartment of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI, United StatesDepartment of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, United StatesDepartment of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, United StatesEllis-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.https://www.frontiersin.org/article/10.3389/fphys.2018.01484/fullEvC syndromeEvc2Limbinciliopathymid-facial defectsskull base |
| spellingShingle | Anshul K. Kulkarni Ke’ale W. Louie Marilia Yatabe Antonio Carlos de Oliveira Ruellas Yoshiyuki Mochida Lucia H. S. Cevidanes Yuji Mishina Honghao Zhang A Ciliary Protein EVC2/LIMBIN Plays a Critical Role in the Skull Base for Mid-Facial Development Frontiers in Physiology EvC syndrome Evc2 Limbin ciliopathy mid-facial defects skull base |
| title | A Ciliary Protein EVC2/LIMBIN Plays a Critical Role in the Skull Base for Mid-Facial Development |
| title_full | A Ciliary Protein EVC2/LIMBIN Plays a Critical Role in the Skull Base for Mid-Facial Development |
| title_fullStr | A Ciliary Protein EVC2/LIMBIN Plays a Critical Role in the Skull Base for Mid-Facial Development |
| title_full_unstemmed | A Ciliary Protein EVC2/LIMBIN Plays a Critical Role in the Skull Base for Mid-Facial Development |
| title_short | A Ciliary Protein EVC2/LIMBIN Plays a Critical Role in the Skull Base for Mid-Facial Development |
| title_sort | ciliary protein evc2 limbin plays a critical role in the skull base for mid facial development |
| topic | EvC syndrome Evc2 Limbin ciliopathy mid-facial defects skull base |
| url | https://www.frontiersin.org/article/10.3389/fphys.2018.01484/full |
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