The emerging roles of ribosome biogenesis in craniofacial development

Abstract

Neural crest cells (NCCs) are a transient, migratory cell population, which originates during neurulation at the neural folds and contributes to the majority of tissues, including the mesenchymal structures of the craniofacial skeleton. The deregulation of the complex developmental processes that guide migration, proliferation, and differentiation of NCCs may result in a wide range of pathological conditions grouped together as neurocristopathies. Recently, due to their multipotent properties neural crest stem cells have received considerable attention as a possible source for stem cell based regenerative therapies. This exciting prospect underlines the need to further explore the developmental programs that guide NCC differentiation. This review explores the particular importance of ribosome biogenesis defects in this context since a specific interface between ribosomopathies and neurocristopathies exists as evidenced by disorders such as Treacher-Collins-Franceschetti syndrome (TCS) and Diamond-Blackfan anemia (DBA).

Transcriptome Profiling Identifies Ribosome Biogenesis as a Target of Alcohol Teratogenicity and Vulnerability during Early Embryogenesis

“…We tested candidate genes in zebrafish, which is amenable to genetic manipulation, has proven utility to evaluate alcohol-sensitive genetic loci [8,17], and undergoes the same calcium/CaMKII-dependent apoptosis as the chick embryo at comparable developmental stages [12]. We focused on ribosomal protein genes because they were the most significantly overrepresented KEGG pathway (Table 2), and they contribute to neural crest development [34]. We selected three ribosomal proteins having significantly reduced expression in alcohol-exposed cells and that are linked to facial deficits in Diamond-Blackfan anemia (RPL5; zrpl5a , RPL11/TCEB3; zrpl11 ) [34] or are known to affect facial development (RPS3A; zrps3a ) [27]; the zrpl3a and zrpl11 morphants recapitulate their transgenic insertional or CRISPR mutation [35–37].…”

“…We focused on ribosomal protein genes because they were the most significantly overrepresented KEGG pathway (Table 2), and they contribute to neural crest development [34]. We selected three ribosomal proteins having significantly reduced expression in alcohol-exposed cells and that are linked to facial deficits in Diamond-Blackfan anemia (RPL5; zrpl5a , RPL11/TCEB3; zrpl11 ) [34] or are known to affect facial development (RPS3A; zrps3a ) [27]; the zrpl3a and zrpl11 morphants recapitulate their transgenic insertional or CRISPR mutation [35–37]. To test for gene-alcohol interactions, we employed concentrations of morpholinos and alcohol that, when administered individually, had no or modest effects on craniofacial development.…”

“…Mechanistic insight is provided by demonstrations that hypomorphs in several ribosome protein pathway participants in zebrafish ( zrps3a , zrpl5a , zrpl11 , mars ; [17] and herein) have greater vulnerability to alcohol-induced apoptosis and craniofacial malformations. Genetic loss-of-function in ribosome biogenesis is also causative in several syndromes that feature craniofacial dysmorphology [34]. In Diamond-Blackfan Anemia, loss-of-function in RPL5, L11 or L26, or RPS7, S17, S19, or S26 is associated with Cathie facies, short stature, and upper limb, heart, and urogenital anomalies [38].…”

Pathways to Specialized Ribosomes: The Brussels Lecture

“…The first identification of the gene responsible for one of these diseases, Diamond Blackfan Anemia, was the ribosomal protein coding gene RPS19 [26] (encoding eS19, [15]), leading this class of diseases to be termed “ribosomopathies”. The list of ribosomopathies has expanded to include diseases caused by mutations in genes that encode ribosomal proteins, ribosome biogenesis factors, and the machinery that modifies ribosomal RNAs (reviewed in [27–31]). Intriguingly, while all of these diseases originate with the ribosome, each has its unique clinical presentation: this is consistent with a model in which different cell/tissue types may require different types of ribosomes.…”

The Contributions of the Ribosome Biogenesis Protein Utp5/WDR43 to Craniofacial Development

“…For this review, we focus our discussion concerning the relationship between ribosome biogenesis and craniofacial development on the protein WDR43, also called Utp5, whose significance in craniofacial development has only recently been identified (Zhao et al 2014). Many erudite reviews have explored the connection between other ribosome biogenesis proteins and craniofacial development (Sakai and Trainor 2009;Trainor and Andrews 2013;van Gijn et al 2013;Ross and Zarbalis 2014;Trainor and Merrill 2014).…”