Society of Craniofacial Genetics and Developmental Biology Annual meeting
Dear Supporters of the Society of Craniofacial Genetics and Developmental Biology,
I am writing to provide information about our 36th annual meeting that will be held in Boston, MA on 
Tuesday October 22, 2013 in conjunction with the 63nd Annual Meeting of the American Society of Human 
Genetics. As in previous years, we will hold the SCGDB meeting prior to the larger ASHG convention. 
Drs. Matthew Harris and Patty Purcell graciously accepted our challenge of organizing the meeting this 
Presentations from the 2015 Annual Meeting

We have edited the webcast from the public portion of the FaceBase Annual Meeting held on Thursday, January 8, 2015 in Marina del Rey, CA and made a video for each presentation in the playlist below:


The presentations are also available in PDF format:  

2015 FaceBase Annual Meeting in Marina del Rey, CA

The next annual meeting of the FaceBase Consortium will be held January 8-9 in Marina del Rey, California. We are pleased to announce that this year the first day of the meeting -- Thursday, January 8th -- will be open to the general craniofacial research community.
During this day-long meeting, each FaceBase project will introduce themselves and describe the research goals they will accomplish through FaceBase. The Hub Coordinating Center will also give an overview of the new FaceBase website and data browser that will be unveiled in 2015.

Facebase 2 Coordinating Center

The FaceBase consortium is a distributed network of researchers investigating craniofacial development and dysmorphology. The consortium includes research projects directly participating via funded ""spoke"" projects as well as members of the craniofacial research community at large. The collection, sharing and integration of heterogeneous data, including genetic, imaging, and anatomical, from human and animal models are essential for advancing craniofacial research.


We will develop and maintain a FaceBase 2 Data Management and Integration Hub infrastructure that will properly store, represent, and serve these data to the research community, and in addition provide access to tools for visualizing, integrating, annotating, linking and analyzing the data. Our three broad aims will provide not only the needed data migration and management, but also a set of user-centered tools for data visualization, comparison and annotation. These are:


Aim 1: Create an infrastructure driven by principles of ease of use and user centered design to manage data throughout its lifecycle. By taking a user centric approach and supporting the use of data throughout its lifecycle, the rate of discovery and utility of the hub can be maximized.


Aim 2: Provide tools within the Hub that accelerate craniofacial research by enabling data annotation, integration and analysis. To maximize the utility of the Hub for both spoke projects and outside users, our proposed infrastructure will allow any user to define a personal workspace and organize datasets, visualization tools, and analysis tools into specific user-driven workflows.


Aim 3: Promote use and collaboration across the FaceBase research network. The Hub will provide a wide range of collaboration tools and services to the consortium as well as organizing face-to-face meetings in order to enhance collaboration. We have assembled an experienced team of experts in bioinformatics, imaging, genetics, mouse and human studies, including FaceBase participants who bring firsthand knowledge of the needs within the craniofacial research community. The FaceBase team is intentionally diverse, to provide each spoke group at least one informed contact who will play an integral role in the development and implementation of the Hub, thereby ensuring that the data of each spoke project will have maximum impact on the community of researchers

Transcriptome Atlases of the Craniofacial Sutures

Craniofacial sutures are the fibrous joints between bones, allowing growth of the skull from prenatal to postnatal development until adult size is achieved. Proper suture development is crucial because abnormal suture fusion can require major surgical intervention to restore a satisfactory head and facial appearance and to prevent secondary damage to the brain, eyes, hearing, breathing, and mastication.


Craniosynostosis, the premature fusion of skull sutures, is a common birth defect, occurring in 1/2500 live births. It may present in syndromic and non-syndromic forms, and while mutations in some of the genes that account for syndromic forms are known, the underlying genetic etiology has not been identified for the majority of cases that are non- syndromic and involve a single suture. A more comprehensive understanding of suture biology and pathology can be aided by knowledge of gene expression profiles of sutures.


Craniofacial sutures vary widely in form, function, and susceptibility to fusion, suggesting that gene expression profiles vary considerably among sutures and during different developmental stages. A detailed characterization of gene expression would require the extraction of specific populations of cells from the different subregions of each suture, including the non-ossifying suture mesenchyme and the flanking osteogenic bone fronts, which are often from distinct bones and may therefore have distinct gene expression patterns.


Our overall goal is to generate comprehensive gene expression atlases of the major and functionally important craniofacial sutures of the mouse, which will accelerate both our understanding of human suture biology and the discovery of candidate genes whose mutation may cause craniosynostosis or other defects of craniofacial bone development. We will apply the state-of-the-art technology of laser capture microdissection to obtain tissue from different craniofacial sutures of both normal and craniosynostotic mouse models, combined with next generation sequencing of extracted RNA (RNA-Seq).


In Aim 1 we will breed a mouse model of Apert syndrome craniosynostosis with the Fgfr2 S252W mutation and use laser capture microdissection to obtain cells from 11 craniofacial sutures from WT and mutant mice. A second mouse model for Saethre-Chotzen syndrome with a Twist1 heterozygous null mutation will be bred to provide a comparison for two major sutures.


In Aim 2 we will extract RNA from the different sutural subregions of WT mice and perform RNA-Seq to generate a comprehensive set of gene expression atlases for normal sutures.


In Aim 3 we will similarly extract RNA from the suture subregions of Apert and Saethre-Chotzen syndrome mice for RNA-Seq and generate gene expression atlases complementary to the normal gene expression atlases.


These atlases will allow the rapid discovery of genes not yet known to be expressed in sutures, reveal the commonalities and differences between sutures that may suggest new hypotheses of suture formation and differentiation, with wider significance for evolutionary studies of the vertebrate skull, and provide insight into the pathology of suture fusion.          

Rapid Identification and Validation of Human Craniofacial Development Genes

The advent of new genomic sequencing technologies has made the task of gene discovery in human developmental disorders highly efficient. Simultaneously, advances in gene targeting in model organisms, specifically in zebrafish, have made semi-high throughput validation and analysis of human candidate genes feasible, including those responsible for craniofacial disorders. This application for a new spoke project in FaceBase 2 will take advantage of this convergence of new technologies to identify and functionally validate approximately two dozen genes involved in novel aspects of human craniofacial development.


Specifically, we will take advantage of already ascertained collections of craniofacial dysmorphoses from Boston Children's Hospital (BCH) and from King Faisal Specialist Hospital and Research Center (KFSHRC) in Saudi Arabia, where the high incidence of consanguinity makes autozygosity mapping and the identification of recessive causal loci highly feasible. We will extend the work of FaceBase beyond its current focus on disorders of palatal development by including a relatively wide range of craniofacial disorders that involve other components of the craniofacial complex. In addition, use of resources already compiled by FaceBase, including detailed gene expression data in mouse and zebrafish, enhancer analyses, and genome wide association studies, in combination with the present data and publicly available datasets, will further facilitate the functional annotation of these newly validated gene. To provide valuable deliverable resources to other FaceBase investigators and to the community at large, we will pursue three Specific Aims.


In Aim 1, we will ascertain and recruit patients with a wide range of craniofacial dysmorphoses of likely monogenic etiology. These patients will not only be identified at the BCH and KFSHRC referral centers, but also solicited from other clinical investigators and potentially even the FaceBase Biorepository.


In Aim 2, patients will be prioritized for further study based on the genetic likelihood of identifying a caual variant. We will then perform whole exome and in some cases whole genome sequence (WES/WGS) analysis, on the proband and potentially other family members, using aCGH to ensure genomic integrity and autozygosity mapping where applicable. An existing state-of-the-art computational pipeline will be used to derive a limited set of potentially causal DNA sequence variants and candidate genes.


Lastly, in Aim 3, in cases where causation cannot be readily established from known function and expression data, we will seek additional independent confirmatory cases and, in parallel, employ a rapid analysis strategy consisting of high-throughput gene expression analysis, morpholino knockdown, and mutagenesis and transgenesis to prepare GOF and LOF alleles. The results will be forwarded to the FaceBase 2 Coordinating Center, with the key deliverables to the community being a validated gene list of human craniofacial developmental regulatory genes and a set of corresponding zebrafish mutants that can be widely shared for further detailed study.          

Developing 3D Craniofacial Morphometry Data and Tools to Transform Dysmorphology

Dysmorphology is the branch of pediatrics and clinical genetics concerned with structural birth defects and delineation of syndromes. More than 1500 syndromes that include orofacial dysmorphia have been described. Today, dysmorphology remains largely descriptive, with diagnoses based on subjective or semi-quantitative clinical impressions of facial and other anatomic features.


Over the past decade, dramatic technological advances in imaging, quantification, and analysis of variation in complex three-dimensional (3D) shape have revolutionized the assessment of morphologic variation, permitting robust definition of quantitative morphometric phenotypes that can distinguish patients from controls in a variety of syndromes.


The goal of this application is to develop systems that will enable diagnostic application of craniofacial 3D morphometrics in clinical practice. We aim to define specific quantitative measures that characterize the aberrant facial shapes in a large number of human dysmorphic syndromes.


Specifically, we aim to build a broad and deep 3D morphometric facial scan ""library"" of defined craniofacial dysmorphic syndromes, a resource that can be shared with approved investigators for research purposes via the NIDCR FaceBase Hub; to develop 3D geometric morphometric (GM) and dense surface modeling (DSM) analytical tools to systematically analyze and distinguish dysmorphic syndromes from unaffected individuals and from each other; and finally to develop a functional, automated, prototype clinical tool that is capable of simultaneously distinguishing a large number of syndromes, and that thereby can assist real-time diagnosis of syndromes in the clinical setting.


We anticipate that 3D photomorphometric ""deep-phenotyping"", in conjunction with the rapid advent of exome and genome sequencing in clinical medicine, will transform dysmorphology from a clinical art into a medical science.  

Anatomical Atlas and Transgenic Toolkit for Late Skull Formation in Zebrafish

The final form of the adult skull is achieved through a complex series of morphogenetic events and growth, largely during post-embryonic development. Many common human congenital defects in the skull have their foundation in these developmental events. The treatment options in human patients are far from perfect, and improvements demand a more complete understanding of the biology underlying post-embryonic skull formation. However, by their complex development and relatively late occurrence, these clinically relevant stages in skull development have been less accessible in experimental organisms.


The zebrafish displays fundamental similarity in skeletogenesis to mammals, including in formation of the vault of the skull and the cranial sutures. Although the later events of skull and suture formation have been relatively less well studied in zebrafish, they are nonetheless accessible for manipulations and imaging, making the zebrafish an ideal system to further our understanding of these complex events. Through a set of interconnected Aims, we propose to establish and make available to the community tools that will lay the foundation for the use of zebrafish to examine skull and suture formation.


We will first construct an online, interactive atlas of normal skull development, encompassing the stages during which the vault of the skull is forming. The foundation of the atlas will be images generated by high-resolution computed tomography (micro-CT), which will be annotated and available for download. These will be complemented by images of transgenic zebrafish expressing fluorophores in critical cell populations, such as chondrocytes and osteoblasts at different stages of development.


For the transgenics, we will optimize recently developed methods for fixation and clearing of large (>1 mM) tissue samples and use a versatile zoom macro-confocal scope. This approach will allow creation of lower resolution data sets from which we can generate three-dimensional reconstructions of gene expression in an entire skull, and will also allow high resolution imaging of specific structures.


The transgenic lines used for the imaging studies will also serve as the basis for a transgenic system, using phiC31 recombinase, to allow replacement of the transgene coding sequences in genomic context while preserving tissue-specific expression patterns; the reagents (fish lines and plasmids) will available to the community.


Finally, both of the laboratories in this application are engaged in ongoing genetic screens to identify mutations causing defects in the juvenile or adult skull. Using a select set of  mutants with clinically relevant phenotypes, we will apply the imaging approaches above to describe the defects in morphology and gene expression during skull development.


Through the combined generation of a comprehensive atlas and a set of transgenic and genetic tools, we will substantially advance the use of zebrafish in the study of skull development, and greatly facilitate comparative studies with mammals that will advance treatment options in human patients.      

Epigenetic Landscapes and Regulatory Divergence of Human Craniofacial Traits

During development, cranial Neural Crest Cells (cNCCs) play major roles in establishing craniofacial morphology and determining its species-specific variation. To understand human distinctive features it is imperative to study human cNCCs and their derivatives in addition to cNCCs from model organisms. Since human NC formation occurs at 3 to 6 weeks of gestation and is largely inaccessible to genetic studies, we have established a human pluripotent stem cell-based cNCC differentiation model in the dish with high relevance to craniofacial development. Moreover, we have extended our model to chimpanzee cNCCs, allowing us to identify molecular features that distinguish human cNCCs from those of our closest evolutionary cousins.


First, we propose to characterize epigenetic landscapes and transcriptomes of human and chimpanzee cNCCs and to identify conserved and species-specific cis-regulatory elements utilized by this unique cell type. Since chromatin modification maps from NCCs of any organism are not yet publicly available beyond our report, we will generate chromatin marking profiles from a cohort of human and chimp post- migratory cNCCs, complemented with transcriptome analyses. Thus, we will create ""reference epigenomes"" that will be annotated for active and poised enhancers and promoters. We have already identified over 2000 regulatory elements that show strong species-specific bias in their chromatin marks in human versus chimpanzee, arguing that human-specific cNCC molecular features do exist and may underlie human-specific craniofacial divergence. These datasets will provide a rich resource for future investigations of the transcriptional and epigenetic basis of human craniofacial evolution, development, and disease.


Second, we will analyze candidate human-specific craniofacial enhancer activity in vivo. To this end, transgenic reporter assays in mouse embryos will be used to analyze the activity of 50 human regulatory elements that either gained or lost active enhancer signature in human cNCCs, as compared to the 50 orthologous chimpanzee regions. Thus, we will generate a validated set of human-specific craniofacial enhancers that can be further explored in mechanistic studies. For 10 selected human-specific enhancers exhibiting gain or loss of activity, interesting activity patterns, or relevant associatin with craniofacial development or disease in humans, we will utilize BAC recombineering to further develop founder transgenic lines that will be distributed to the craniofacial community.   


How to access FaceBase Data?

FaceBase Data fits into one of two broad categories: open and restricted access. Open-access data is available on the FaceBase website to any interested user and does not require any formal registration. Open-access data is limited to summary-level human data (ex: averaged facial measures), and all non-human data.  In contrast, all individual-level human data (ex: demographic descriptors, phenotypic measures, 3D images) is restricted access data and requires the requestor to complete and submit the Data Access Request form found in the Official Documents.

How to contribute data to FaceBase?

The FaceBase Consortium’s goal is to develop a resource for the craniofacial research community, with a current focus on mid-face development and orofacial clefts. The highest priority is making data from FaceBase projects broadly available through the FaceBase website. We also welcome submissions of high-quality, well-documented datasets from non-FaceBase projects. Of particular interest are data from peer-reviewed publications that are relevant to FaceBase’s current focus on mid-face development and orofacial clefts. Unpublished data relevant to FaceBase’s current focus will also be considered, especially those that would otherwise be very difficult for the craniofacial research community to obtain (e.g., data from rare craniofacial conditions) or that are suitable for secondary or integrative analyses (e.g., RNA-seq, genotyping, or large-scale expression data). If you would like to know more about making data from your project available through FaceBase, please see the menu... more

How to request access to restricted human data?

  1. Complete the FaceBase Data Use Certification Agreement.
  2. Complete the Data Access Request (DAR) document, and an IRB approval from your institution. 
  3. Submit the Data Use Certification Agreement, DAR, and the IRB approval to the NIH Data Access Committee at
    You shall receive an answer from the Data Access Committee within 4-6 weeks.
  4. Once your request is processed, you are notified via email that your user account is approved for human dataset downloads. Note that this permission to download human data expires 180 days after the date of approval.

If you have... more