Shared molecular networks in orofacial and neural tube development

• Published in: Birth defects research Vol. 109; no. 2; p. 169
• Main Authors: Kousa, Youssef A, Mansour, Tamer A, Seada, Haitham, Matoo, Samaneh, Schutte, Brian C
• Format: Journal Article
• Language: English
• Published: United States 30.01.2017
• Subjects: Abnormalities, Multiple - genetics; Abnormalities, Multiple - metabolism; Abnormalities, Multiple - pathology; Animals; Cleft Lip - genetics; Cleft Lip - metabolism; Cleft Lip - pathology; Cleft Palate - genetics; Cleft Palate - metabolism; Cleft Palate - pathology; Computational Biology; Data Mining; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Embryonic Development - genetics; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Humans; Interferon Regulatory Factors - genetics; Interferon Regulatory Factors - metabolism; Mice; Mutation; Neural Tube - abnormalities; Neural Tube - growth & development; Neural Tube - metabolism; Neural Tube Defects - genetics; Neural Tube Defects - metabolism; Neural Tube Defects - pathology; Neurulation - genetics; Organogenesis - genetics; Signal Transduction; Transcription Factor AP-2 - genetics; Transcription Factor AP-2 - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; TFAP2A; mouse models; human genetics; CLP; embryonic development; spina bifida; Van der Woude Syndrome; orofacial clefts; cleft palate; GRHL3; neural tube defects; popliteal pterygium syndrome; cleft lip; cleft lip and palate; IRF6
• ISSN: 2472-1727
• DOI: 10.1002/bdra.23598

Single genetic variants can affect multiple tissues during development. Thus it is possible that disruption of shared gene regulatory networks might underlie syndromic presentations. In this study, we explore this idea through examination of two critical developmental programs that control orofacial and neural tube development and identify shared regulatory factors and networks. Identification of these networks has the potential to yield additional candidate genes for poorly understood developmental disorders and assist in modeling and perhaps managing risk factors to prevent morbidly and mortality. We reviewed the literature to identify genes common between orofacial and neural tube defects and development. We then conducted a bioinformatic analysis to identify shared molecular targets and pathways in the development of these tissues. Finally, we examine publicly available RNA-Seq data to identify which of these genes are expressed in both tissues during development. We identify common regulatory factors in orofacial and neural tube development. Pathway enrichment analysis shows that folate, cancer and hedgehog signaling pathways are shared in neural tube and orofacial development. Developing neural tissues differentially express mouse exencephaly and cleft palate genes, whereas developing orofacial tissues were enriched for both clefting and neural tube defect genes. These data suggest that key developmental factors and pathways are shared between orofacial and neural tube defects. We conclude that it might be most beneficial to focus on common regulatory factors and pathways to better understand pathology and develop preventative measures for these birth defects. Birth Defects Research 109:169-179, 2017. © 2016 Wiley Periodicals, Inc.