Utilizing the chicken as an animal model for human craniofacial ciliopathies

Schock, Elizabeth N.; Chang, Che Shoa; Youngworth, Ingrid; Davey, Megan; Delany, Mary E.; Brugmann, Samantha A.

doi:10.1016/j.ydbio.2015.10.024

Cited by 31 publications

(37 citation statements)

References 108 publications

(127 reference statements)

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“…Aglossia is a rare condition frequently associated with syndromes that affect development of the craniofacial complex (Emmanouil-Nikoloussi and Kerameos-Foroglou, 1992), including ciliopathies (Chang et al, 2015; Schock et al, 2016; Zaghloul and Brugmann, 2011). Interestingly, there are now several transgenic lines with impaired transduction of major signaling pathways that results in glossal anomalies (Barron et al, 2011; Han et al, 2012; Jeong et al, 2004; Parada and Chai, 2015; Parada et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Cilia-dependent GLI processing in neural crest cells is required for tongue development

Millington¹,

Elliott²,

Chang³

et al. 2017

Developmental Biology

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Ciliopathies are a class of diseases caused by the loss of a ubiquitous, microtubule-based organelle called a primary cilium. Ciliopathies commonly result in defective development of the craniofacial complex, causing midfacial defects, craniosynostosis, micrognathia and aglossia. Herein, we explored how the conditional loss of primary cilia on neural crest cells (Kif3af/f;Wnt1-Cre) generated aglossia. On a cellular level, our data revealed that aglossia in Kif3af/f;Wnt1-Cre embryos was due to a loss of mesoderm-derived muscle precursors migrating into and surviving in the tongue anlage. To determine the molecular basis for this phenotype, we performed RNA-seq, in situ hybridization, qPCR and Western blot analyses. We found that transduction of the Sonic hedgehog (Shh) pathway, rather than other pathways previously implicated in tongue development, was aberrant in Kif3af/f;Wnt1-Cre embryos. Despite increased production of full-length GLI2 and GLI3 isoforms, previously identified GLI targets important for mandibular and glossal development (Foxf1, Foxf2, Foxd1 and Foxd2) were transcriptionally downregulated in Kif3af/f;Wnt1-Cre embryos. Genetic removal of GLI activator (GLIA) isoforms in neural crest cells recapitulated the aglossia phenotype and downregulated Fox gene expression. Genetic addition of GLIA isoforms in neural crest cells partially rescued the aglossia phenotype and Fox gene expression in Kif3af/f;Wnt1-Cre embryos. Together, our data suggested that glossal development requires primary cilia-dependent GLIA activity in neural crest cells. Furthermore, these data, in conjunction with our previous work, suggested prominence specific roles for GLI isoforms; with development of the frontonasal prominence relying heavily on the repressor isoform and the development of the mandibular prominence/tongue relying heavily on the activator isoform.

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Section: Discussionmentioning

confidence: 99%

Cilia-dependent GLI processing in neural crest cells is required for tongue development

Millington¹,

Elliott²,

Chang³

et al. 2017

Developmental Biology

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“…The talpid mutants [talpid, talpid2 (ta2), talpid3 (ta3)] are categorized together due to their shared phenotype of polydactyly and severe craniofacial malformations (Schock et al, 2016). After many years of work, the Edinburgh group who spearheaded many of the early efforts to create genomic resources for the chicken, finally mapped and identified the gene underlying the talpid3 line (KIAA0586) (Davey et al, 2006, Yin et al, 2009).…”

Section: Abnormal Craniofacial Development In Spontaneous Chicken Mutmentioning

confidence: 99%

Craniofacial development: discoveries made in the chicken embryo

Abramyan¹,

Richman²

2018

Int. J. Dev. Biol.

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The aim of this review is to highlight some of the key contributions to our understanding of craniofacial research from work carried out with the chicken and other avian embryos. From the very first observations of neural crest cell migration to the fusion of the primary palate, the chicken has proven indispensable in facilitating craniofacial research. In this review we will look back to the premolecular studies where "cut and paste" grafting experiments mapped the fate of cranial neural crest cells, the role of different tissue layers in patterning the face, and more recently the contribution of neural crest cells to jaw size and identity. In the late 80's the focus shifted to the molecular underpinnings of facial development and, in addition to grafting experiments, various chemicals and growth factors were being applied to the face. The chicken is above all else an experimental model, inviting hands-on manipulations. We describe the elegant discoveries made by directly controlling signaling either in the brain, in the pharyngeal arches or in the face itself. We cover how sonic hedgehog (Shh) signals to the face and how various growth factors regulate facial prominence identity, growth and fusion. We also review abnormal craniofacial development and how several type of spontaneous chicken mutants shed new light on diseases affecting the primary cilium in humans. Finally, we bring out the very important role that the bird beak has played in understanding amniote evolution. The chicken, duck and quail have been and will continue to be used as experimental models to explore the evolution of jaw diversity and the morphological constraints of the vertebrate face.

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“…Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant disorder where patients are predisposed to kidney cancer, lung and kidney cysts and benign skin tumors [108]. Less common ciliopathies are some of the oral-facial-digital (OFD) syndromes, such as Joubert syndrome, Meckel-Gruber syndrome and orofaciodigital syndrome type 1 [109-113]. Other ciliopathies include, but are not limited to retinal dystrophies, such as Leber's congenital amaurosis [114], Senior–Løken syndrome [115], Bardet–Biedl syndrome [116, 117], Alström syndrome [118] and other types of nephronophthisis [119].…”

Section: Aurka Ciliopathies and Cancermentioning

confidence: 99%

Mechanisms for nonmitotic activation of Aurora-A at cilia

Korobeynikov

Deneka

Golemis

2017

Biochemical Society Transactions

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Overexpression of the Aurora-A (AURKA) kinase is oncogenic in many tumors. Many studies of AURKA have focused on activities of this kinase in mitosis, and elucidated the mechanisms by which AURKA activity is induced at the G2/M boundary through interactions with proteins such as TPX2 and NEDD9. These studies have informed the development of small molecule inhibitors of AURKA, of which a number are currently under preclinical and clinical assessment. While the first activities defined for AURKA were its control of centrosomal maturation and organization of the mitotic spindle, an increasing number of studies over the past decade have recognized a separate biological function of AURKA, in controlling disassembly of the primary cilium, a small organelle protruding from the cell surface that serves as a signaling platform. Importantly, these activities require activation of AURKA in early G1, and the mechanisms of activation are much less well defined than those in mitosis. Better understanding of the control of AURKA activity, and the role of AURKA at cilia, are both important in optimizing the efficacy and interpreting potential downstream consequences of AURKA inhibitors in the clinic. We here provide a current overview of proteins and mechanisms that have been defined as activating AURKA in G1, based on study of ciliary disassembly.

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Utilizing the chicken as an animal model for human craniofacial ciliopathies

Cited by 31 publications

References 108 publications

Cilia-dependent GLI processing in neural crest cells is required for tongue development

Cilia-dependent GLI processing in neural crest cells is required for tongue development

Craniofacial development: discoveries made in the chicken embryo

Mechanisms for nonmitotic activation of Aurora-A at cilia

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