Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
3.7
2.7
Journals
JDB
Special Issues
Craniofacial Genetics and Developmental Biology
share announcement

Craniofacial Genetics and Developmental Biology

A special issue of Journal of Developmental Biology (ISSN 2221-3759).

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 56945

Special Issue Editors

Prof. Dr. Sally A. Moody

E-Mail Website
Guest Editor
Department of Anatomy and Cell Biology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
Interests: neural fate specification; Craniofacial development; cranial sensory placodes; Six1; neural gene regulatory networks
Special Issues, Collections and Topics in MDPI journals
Dr. André Luiz Pasqua Tavares

E-Mail Website
Co-Guest Editor
Department of Anatomy and Cell Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA
Interests: craniofacial; development; SIX1; BOR; embryology; placodes; neural crest; birth defects

Special Issue Information

Dear Colleagues,

The majority of human birth defects include craniofacial dysmorphologies. Key to their prevention, early detection and clinical amelioration is research into the underlying genetic causes, as well as an understanding of the normal developmental processes that give rise to the large variety of craniofacial structures. Using human sequencing data and several animal model systems, significant progress is being made into the fundamental developmental genetics and morphogenesis of these tissues. This Special Issue of the Journal of Developmental Biology will provide an overview of the current standing of basic and clinical research in craniofacial genetics and developmental biology, highlighting directions for future craniofacial research and clinical translation. Contributions can be reviews, as well as research papers.

Prof. Sally Moody
Guest Editor
Dr. André Luiz Pasqua Tavares
Co-Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Developmental Biology is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cranial neural crest
  • Cranial sensory placodes
  • Cleft lip
  • Cleft palate
  • Craniofacial syndromes
  • Mandible
  • Maxilla
  • Teeth
  • Calvarium
  • Auditory-vestibular

Published Papers (13 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review, Other

4 pages, 165 KiB  
Editorial
Advances in Understanding the Pathogenesis of Craniofacial Birth Defects
by Andre L. P. Tavares and Sally A. Moody
J. Dev. Biol. 2022, 10(3), 27; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb10030027 - 01 Jul 2022
Viewed by 2095
Abstract
Each year approximately 35% of babies are born with craniofacial abnormalities of the skull, jaws, ears, and/or teeth, which in turn can lead to problems in feeding, hearing, and sight [...] Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)

Research

Jump to: Editorial, Review, Other

10 pages, 1961 KiB  
Communication
R-Spondin 3 Regulates Mammalian Dental and Craniofacial Development
by Krishnakali Dasgupta, Jeffry M. Cesario, Sara Ha, Kesava Asam, Lindsay J. Deacon, Ana H. Song, Julie Kim, John Cobb, Jeong Kyo Yoon and Juhee Jeong
J. Dev. Biol. 2021, 9(3), 31; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9030031 - 12 Aug 2021
Cited by 3 | Viewed by 3560
Abstract
Development of the teeth requires complex signaling interactions between the mesenchyme and the epithelium mediated by multiple pathways. For example, canonical WNT signaling is essential to many aspects of odontogenesis, and inhibiting this pathway blocks tooth development at an early stage. R-spondins (RSPOs) [...] Read more.
Development of the teeth requires complex signaling interactions between the mesenchyme and the epithelium mediated by multiple pathways. For example, canonical WNT signaling is essential to many aspects of odontogenesis, and inhibiting this pathway blocks tooth development at an early stage. R-spondins (RSPOs) are secreted proteins, and they mostly augment WNT signaling. Although RSPOs have been shown to play important roles in the development of many organs, their role in tooth development is unclear. A previous study reported that mutating Rspo2 in mice led to supernumerary lower molars, while teeth forming at the normal positions showed no significant anomalies. Because multiple Rspo genes are expressed in the orofacial region, it is possible that the relatively mild phenotype of Rspo2 mutants is due to functional compensation by other RSPO proteins. We found that inactivating Rspo3 in the craniofacial mesenchyme caused the loss of lower incisors, which did not progress beyond the bud stage. A simultaneous deletion of Rspo2 and Rspo3 caused severe disruption of craniofacial development from early stages, which was accompanied with impaired development of all teeth. Together, these results indicate that Rspo3 is an important regulator of mammalian dental and craniofacial development. Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)
►▼ Show Figures

Figure 1

18 pages, 5525 KiB  
Article
A Novel Mutation in Cse1l Disrupts Brain and Eye Development with Specific Effects on Pax6 Expression
by Lauren E. Blizzard, Chelsea Menke, Shaili D. Patel, Ronald R. Waclaw, Salil A. Lachke and Rolf W. Stottmann
J. Dev. Biol. 2021, 9(3), 27; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9030027 - 07 Jul 2021
Cited by 1 | Viewed by 3205
Abstract
Forward genetics in the mouse continues to be a useful and unbiased approach to identifying new genes and alleles with previously unappreciated roles in mammalian development and disease. Here, we report a new mouse allele of Cse1l that was recovered from an ENU [...] Read more.
Forward genetics in the mouse continues to be a useful and unbiased approach to identifying new genes and alleles with previously unappreciated roles in mammalian development and disease. Here, we report a new mouse allele of Cse1l that was recovered from an ENU mutagenesis screen. Embryos homozygous for the anteater allele of Cse1l display a number of variable phenotypes, with craniofacial and ocular malformations being the most obvious. We provide evidence that Cse1l is the causal gene through complementation with a novel null allele of Cse1l generated by CRISPR-Cas9 editing. While the variability in the anteater phenotype was high enough to preclude a detailed molecular analysis, we demonstrate a very penetrant reduction in Pax6 levels in the developing eye along with significant ocular developmental phenotypes. The eye gene discovery tool iSyTE shows Cse1l to be significantly expressed in the lens from early eye development stages in embryos through adulthood. Cse1l has not previously been shown to be required for organogenesis as homozygosity for a null allele results in very early lethality. Future detailed studies of Cse1l function in craniofacial and neural development will be best served with a conditional allele to circumvent the variable phenotypes we report here. We suggest that human next-generation (whole genome or exome) sequencing studies yielding variants of unknown significance in CSE1L could consider these findings as part of variant analysis. Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)
►▼ Show Figures

Figure 1

17 pages, 1987 KiB  
Article
Mutations in SIX1 Associated with Branchio-oto-Renal Syndrome (BOR) Differentially Affect Otic Expression of Putative Target Genes
by Tanya Mehdizadeh, Himani D. Majumdar, Sarah Ahsan, Andre L. P. Tavares and Sally A. Moody
J. Dev. Biol. 2021, 9(3), 25; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9030025 - 30 Jun 2021
Cited by 10 | Viewed by 2983
Abstract
Several single-nucleotide mutations in SIX1 underlie branchio-otic/branchio-oto-renal (BOR) syndrome, but the clinical literature has not been able to correlate different variants with specific phenotypes. We previously assessed whether variants in either the cofactor binding domain (V17E, R110W) or the DNA binding domain (W122R, [...] Read more.
Several single-nucleotide mutations in SIX1 underlie branchio-otic/branchio-oto-renal (BOR) syndrome, but the clinical literature has not been able to correlate different variants with specific phenotypes. We previously assessed whether variants in either the cofactor binding domain (V17E, R110W) or the DNA binding domain (W122R, Y129C) might differentially affect early embryonic gene expression, and found that each variant had a different combination of effects on neural crest and placode gene expression. Since the otic vesicle gives rise to the inner ear, which is consistently affected in BOR, herein we focused on whether the variants differentially affected the otic expression of genes previously found to be likely Six1 targets. We found that V17E, which does not bind Eya cofactors, was as effective as wild-type Six1 in reducing most otic target genes, whereas R110W, W122R and Y129C, which bind Eya, were significantly less effective. Notably, V17E reduced the otic expression of prdm1, whereas R110W, W122R and Y129C expanded it. Since each mutant has defective transcriptional activity but differs in their ability to interact with Eya cofactors, we propose that altered cofactor interactions at the mutated sites differentially interfere with their ability to drive otic gene expression, and these differences may contribute to patient phenotype variability. Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)
►▼ Show Figures

Graphical abstract

18 pages, 7016 KiB  
Article
Wnt-Dependent Activation of ERK Mediates Repression of Chondrocyte Fate during Calvarial Development
by Beatriz A Ibarra, Cody Machen and Radhika P. Atit
J. Dev. Biol. 2021, 9(3), 23; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9030023 - 27 Jun 2021
Cited by 10 | Viewed by 2645
Abstract
Wnt signaling regulates cell fate decisions in diverse contexts during development, and loss of Wnt signaling in the cranial mesenchyme results in a robust and binary cell fate switch from cranial bone to ectopic cartilage. The Extracellular signal-regulated protein kinase 1 and 2 [...] Read more.
Wnt signaling regulates cell fate decisions in diverse contexts during development, and loss of Wnt signaling in the cranial mesenchyme results in a robust and binary cell fate switch from cranial bone to ectopic cartilage. The Extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) and Wnt signaling pathways are activated during calvarial osteoblast cell fate selection. Here, we test the hypothesis that ERK signaling is a mediator of Wnt-dependent cell fate decisions in the cranial mesenchyme. First, we show that loss of Erk1/2 in the cranial mesenchyme results in a diminished domain of osteoblast marker expression and increased expression of cartilage fate markers and ectopic cartilage formation in the frontal bone primordia. Second, we show that mesenchyme Wnt/β-catenin signaling and Wntless are required for ERK activation in calvarial osteoblasts. Third, we demonstrate that Wnt and ERK signaling pathways function together to repress SOX9 expression in mouse cranial mesenchyme. Our results demonstrate an interaction between the Wnt and ERK signaling pathways in regulating lineage selection in a subset of calvarial cells and provide new insights into Wnt-dependent cell fate decisions. Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)
►▼ Show Figures

Figure 1

14 pages, 3803 KiB  
Article
Inhibition of Cyclooxygenase-2 Alters Craniofacial Patterning during Early Embryonic Development of Chick
by Bhaval Parmar, Urja Verma, Kashmira Khaire, Dhanush Danes and Suresh Balakrishnan
J. Dev. Biol. 2021, 9(2), 16; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9020016 - 23 Apr 2021
Cited by 4 | Viewed by 3192
Abstract
A recent study from our lab revealed that the inhibition of cyclooxygenase-2 (COX-2) exclusively reduces the level of PGE2 (Prostaglandin E2) among prostanoids and hampers the normal development of several structures, strikingly the cranial vault, in chick embryos. In order [...] Read more.
A recent study from our lab revealed that the inhibition of cyclooxygenase-2 (COX-2) exclusively reduces the level of PGE2 (Prostaglandin E2) among prostanoids and hampers the normal development of several structures, strikingly the cranial vault, in chick embryos. In order to unearth the mechanism behind the deviant development of cranial features, the expression pattern of various factors that are known to influence cranial neural crest cell (CNCC) migration was checked in chick embryos after inhibiting COX-2 activity using etoricoxib. The compromised level of cell adhesion molecules and their upstream regulators, namely CDH1 (E-cadherin), CDH2 (N-cadherin), MSX1 (Msh homeobox 1), and TGF-β (Transforming growth factor beta), observed in the etoricoxib-treated embryos indicate that COX-2, through its downstream effector PGE2, regulates the expression of these factors perhaps to aid the migration of CNCCs. The histological features and levels of FoxD3 (Forkhead box D3), as well as PCNA (Proliferating cell nuclear antigen), further consolidate the role of COX-2 in the migration and survival of CNCCs in developing embryos. The results of the current study indicate that COX-2 plays a pivotal role in orchestrating craniofacial structures perhaps by modulating CNCC proliferation and migration during the embryonic development of chicks. Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)
►▼ Show Figures

Figure 1

18 pages, 2509 KiB  
Article
Timing of Mouse Molar Formation Is Independent of Jaw Length Including Retromolar Space
by Daisy (Jihyung) Ko, Tess Kelly, Lacey Thompson, Jasmene K. Uppal, Nasim Rostampour, Mark Adam Webb, Ning Zhu, George Belev, Prosanta Mondal, David M. L. Cooper and Julia C. Boughner
J. Dev. Biol. 2021, 9(1), 8; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9010008 - 12 Mar 2021
Cited by 5 | Viewed by 3503
Abstract
For humans and other mammals to eat effectively, teeth must develop properly inside the jaw. Deciphering craniodental integration is central to explaining the timely formation of permanent molars, including third molars which are often impacted in humans, and to clarifying how teeth and [...] Read more.
For humans and other mammals to eat effectively, teeth must develop properly inside the jaw. Deciphering craniodental integration is central to explaining the timely formation of permanent molars, including third molars which are often impacted in humans, and to clarifying how teeth and jaws fit, function and evolve together. A factor long-posited to influence molar onset time is the jaw space available for each molar organ to form within. Here, we tested whether each successive molar initiates only after a minimum threshold of space is created via jaw growth. We used synchrotron-based micro-CT scanning to assess developing molars in situ within jaws of C57BL/6J mice aged E10 to P32, encompassing molar onset to emergence. We compared total jaw, retromolar and molar lengths, and molar onset times, between upper and lower jaws. Initiation time and developmental duration were comparable between molar upper and lower counterparts despite shorter, slower-growing retromolar space in the upper jaw, and despite size differences between upper and lower molars. Timing of molar formation appears unmoved by jaw length including space. Conditions within the dental lamina likely influence molar onset much more than surrounding jaw tissues. We theorize that molar initiation is contingent on sufficient surface area for the physical reorganization of dental epithelium and its invagination of underlying mesenchyme. Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)
►▼ Show Figures

Figure 1

17 pages, 2187 KiB  
Article
Craniofacial Analysis May Indicate Co-Occurrence of Skeletal Malocclusions and Associated Risks in Development of Cleft Lip and Palate
by Denise K. Liberton, Payal Verma, Konstantinia Almpani, Peter W. Fung, Rashmi Mishra, Snehlata Oberoi, Figen Ç. Şenel, James K. Mah, John Huang, Bonnie L. Padwa and Janice S. Lee
J. Dev. Biol. 2020, 8(1), 2; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb8010002 - 28 Jan 2020
Cited by 9 | Viewed by 4106
Abstract
Non-syndromic orofacial clefts encompass a range of morphological changes affecting the oral cavity and the craniofacial skeleton, of which the genetic and epigenetic etiologic factors remain largely unknown. The objective of this study is to explore the contribution of underlying dentofacial deformities (also [...] Read more.
Non-syndromic orofacial clefts encompass a range of morphological changes affecting the oral cavity and the craniofacial skeleton, of which the genetic and epigenetic etiologic factors remain largely unknown. The objective of this study is to explore the contribution of underlying dentofacial deformities (also known as skeletal malocclusions) in the craniofacial morphology of non-syndromic cleft lip and palate patients (nsCLP). For that purpose, geometric morphometric analysis was performed using full skull cone beam computed tomography (CBCT) images of patients with nsCLP (n = 30), normocephalic controls (n = 60), as well as to sex- and ethnicity- matched patients with an equivalent dentofacial deformity (n = 30). Our outcome measures were shape differences among the groups quantified via principal component analysis and associated principal component loadings, as well as mean shape differences quantified via a Procrustes distance among groups. According to our results, despite the shape differences among all three groups, the nsCLP group shares many morphological similarities in the maxilla and mandible with the dentofacial deformity group. Therefore, the dentoskeletal phenotype in nsCLP could be the result of the cleft and the coexisting dentofacial deformity and not simply the impact of the cleft. Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)
►▼ Show Figures

Figure 1

Review

Jump to: Editorial, Research, Other

17 pages, 2164 KiB  
Review
The Skull’s Girder: A Brief Review of the Cranial Base
by Shankar Rengasamy Venugopalan and Eric Van Otterloo
J. Dev. Biol. 2021, 9(1), 3; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9010003 - 23 Jan 2021
Cited by 11 | Viewed by 5141
Abstract
The cranial base is a multifunctional bony platform within the core of the cranium, spanning rostral to caudal ends. This structure provides support for the brain and skull vault above, serves as a link between the head and the vertebral column below, and [...] Read more.
The cranial base is a multifunctional bony platform within the core of the cranium, spanning rostral to caudal ends. This structure provides support for the brain and skull vault above, serves as a link between the head and the vertebral column below, and seamlessly integrates with the facial skeleton at its rostral end. Unique from the majority of the cranial skeleton, the cranial base develops from a cartilage intermediate—the chondrocranium—through the process of endochondral ossification. Owing to the intimate association of the cranial base with nearly all aspects of the head, congenital birth defects impacting these structures often coincide with anomalies of the cranial base. Despite this critical importance, studies investigating the genetic control of cranial base development and associated disorders lags in comparison to other craniofacial structures. Here, we highlight and review developmental and genetic aspects of the cranial base, including its transition from cartilage to bone, dual embryological origins, and vignettes of transcription factors controlling its formation. Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)
►▼ Show Figures

Figure 1

21 pages, 1771 KiB  
Review
Phenotypes, Developmental Basis, and Genetics of Pierre Robin Complex
by Susan M. Motch Perrine, Meng Wu, Greg Holmes, Bryan C. Bjork, Ethylin Wang Jabs and Joan T. Richtsmeier
J. Dev. Biol. 2020, 8(4), 30; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb8040030 - 05 Dec 2020
Cited by 9 | Viewed by 5680
Abstract
The phenotype currently accepted as Pierre Robin syndrome/sequence/anomalad/complex (PR) is characterized by mandibular dysmorphology, glossoptosis, respiratory obstruction, and in some cases, cleft palate. A causative sequence of developmental events is hypothesized for PR, but few clear causal relationships between discovered genetic variants, dysregulated [...] Read more.
The phenotype currently accepted as Pierre Robin syndrome/sequence/anomalad/complex (PR) is characterized by mandibular dysmorphology, glossoptosis, respiratory obstruction, and in some cases, cleft palate. A causative sequence of developmental events is hypothesized for PR, but few clear causal relationships between discovered genetic variants, dysregulated gene expression, precise cellular processes, pathogenesis, and PR-associated anomalies are documented. This review presents the current understanding of PR phenotypes, the proposed pathogenetic processes underlying them, select genes associated with PR, and available animal models that could be used to better understand the genetic basis and phenotypic variation of PR. Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)
►▼ Show Figures

Figure 1

24 pages, 2549 KiB  
Review
Genetics Underlying the Interactions between Neural Crest Cells and Eye Development
by Jochen Weigele and Brenda L. Bohnsack
J. Dev. Biol. 2020, 8(4), 26; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb8040026 - 10 Nov 2020
Cited by 18 | Viewed by 6377
Abstract
The neural crest is a unique, transient stem cell population that is critical for craniofacial and ocular development. Understanding the genetics underlying the steps of neural crest development is essential for gaining insight into the pathogenesis of congenital eye diseases. The neural crest [...] Read more.
The neural crest is a unique, transient stem cell population that is critical for craniofacial and ocular development. Understanding the genetics underlying the steps of neural crest development is essential for gaining insight into the pathogenesis of congenital eye diseases. The neural crest cells play an under-appreciated key role in patterning the neural epithelial-derived optic cup. These interactions between neural crest cells within the periocular mesenchyme and the optic cup, while not well-studied, are critical for optic cup morphogenesis and ocular fissure closure. As a result, microphthalmia and coloboma are common phenotypes in human disease and animal models in which neural crest cell specification and early migration are disrupted. In addition, neural crest cells directly contribute to numerous ocular structures including the cornea, iris, sclera, ciliary body, trabecular meshwork, and aqueous outflow tracts. Defects in later neural crest cell migration and differentiation cause a constellation of well-recognized ocular anterior segment anomalies such as Axenfeld–Rieger Syndrome and Peters Anomaly. This review will focus on the genetics of the neural crest cells within the context of how these complex processes specifically affect overall ocular development and can lead to congenital eye diseases. Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)
►▼ Show Figures

Graphical abstract

27 pages, 1725 KiB  
Review
Cranial Neural Crest Cells and Their Role in the Pathogenesis of Craniofacial Anomalies and Coronal Craniosynostosis
by Erica M. Siismets and Nan E. Hatch
J. Dev. Biol. 2020, 8(3), 18; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb8030018 - 09 Sep 2020
Cited by 28 | Viewed by 8671
Abstract
Craniofacial anomalies are among the most common of birth defects. The pathogenesis of craniofacial anomalies frequently involves defects in the migration, proliferation, and fate of neural crest cells destined for the craniofacial skeleton. Genetic mutations causing deficient cranial neural crest migration and proliferation [...] Read more.
Craniofacial anomalies are among the most common of birth defects. The pathogenesis of craniofacial anomalies frequently involves defects in the migration, proliferation, and fate of neural crest cells destined for the craniofacial skeleton. Genetic mutations causing deficient cranial neural crest migration and proliferation can result in Treacher Collins syndrome, Pierre Robin sequence, and cleft palate. Defects in post-migratory neural crest cells can result in pre- or post-ossification defects in the developing craniofacial skeleton and craniosynostosis (premature fusion of cranial bones/cranial sutures). The coronal suture is the most frequently fused suture in craniosynostosis syndromes. It exists as a biological boundary between the neural crest-derived frontal bone and paraxial mesoderm-derived parietal bone. The objective of this review is to frame our current understanding of neural crest cells in craniofacial development, craniofacial anomalies, and the pathogenesis of coronal craniosynostosis. We will also discuss novel approaches for advancing our knowledge and developing prevention and/or treatment strategies for craniofacial tissue regeneration and craniosynostosis. Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)
►▼ Show Figures

Graphical abstract

Other

18 pages, 5569 KiB  
Case Report
Quantitative Craniofacial Analysis and Generation of Human Induced Pluripotent Stem Cells for Muenke Syndrome: A Case Report
by Fahad K. Kidwai, Byron W. H. Mui, Konstantinia Almpani, Priyam Jani, Cyrus Keyvanfar, Kulsum Iqbal, Sriram S. Paravastu, Deepika Arora, Pamela Orzechowski, Randall K. Merling, Barbara Mallon, Vamsee D. Myneni, Moaz Ahmad, Paul Kruszka, Maximilian Muenke, Jeremiah Woodcock, Jeffrey W. Gilman, Pamela G. Robey and Janice S. Lee
J. Dev. Biol. 2021, 9(4), 39; https://0-doi-org.brum.beds.ac.uk/10.3390/jdb9040039 - 22 Sep 2021
Cited by 4 | Viewed by 3373
Abstract
In this case report, we focus on Muenke syndrome (MS), a disease caused by the p.Pro250Arg variant in fibroblast growth factor receptor 3 (FGFR3) and characterized by uni- or bilateral coronal suture synostosis, macrocephaly without craniosynostosis, dysmorphic craniofacial features, and dental malocclusion. The [...] Read more.
In this case report, we focus on Muenke syndrome (MS), a disease caused by the p.Pro250Arg variant in fibroblast growth factor receptor 3 (FGFR3) and characterized by uni- or bilateral coronal suture synostosis, macrocephaly without craniosynostosis, dysmorphic craniofacial features, and dental malocclusion. The clinical findings of MS are further complicated by variable expression of phenotypic traits and incomplete penetrance. As such, unraveling the mechanisms behind MS will require a comprehensive and systematic way of phenotyping patients to precisely identify the impact of the mutation variant on craniofacial development. To establish this framework, we quantitatively delineated the craniofacial phenotype of an individual with MS and compared this to his unaffected parents using three-dimensional cephalometric analysis of cone beam computed tomography scans and geometric morphometric analysis, in addition to an extensive clinical evaluation. Secondly, given the utility of human induced pluripotent stem cells (hiPSCs) as a patient-specific investigative tool, we also generated the first hiPSCs derived from a family trio, the proband and his unaffected parents as controls, with detailed characterization of all cell lines. This report provides a starting point for evaluating the mechanistic underpinning of the craniofacial development in MS with the goal of linking specific clinical manifestations to molecular insights gained from hiPSC-based disease modeling. Full article
(This article belongs to the Special Issue Craniofacial Genetics and Developmental Biology)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-13
Back to TopTop