biostudies-literatureFalcon KTStowers Institute for Medical ResearchNIDCR NIH HHSAmerican Association for AnatomyHHS | NIH | National Institute of Dental and Craniofacial ResearchNIGMS NIH HHSe2116974119https://www.ebi.ac.uk/biostudies/studies/S-EPMC9351356biostudies-literatureUnknown119(31)Ribosomal RNA (rRNA) transcription by RNA polymerase I (Pol I) is a critical rate-limiting step in ribosome biogenesis, which is essential for cell survival. Despite its global function, disruptions in ribosome biogenesis cause tissue-specific birth defects called ribosomopathies, which frequently affect craniofacial development. Here, we describe a cellular and molecular mechanism underlying the susceptibility of craniofacial development to disruptions in Pol I transcription. We show that Pol I subunits are highly expressed in the neuroepithelium and neural crest cells (NCCs), which generate most of the craniofacial skeleton. High expression of Pol I subunits sustains elevated rRNA transcription in NCC progenitors, which supports their high tissue-specific levels of protein translation, bProceedings of the National Academy of Sciences of the United States of AmericaDynamic regulation and requirement for ribosomal RNA transcription during mammalian development.PMC9351356DE030972P20 GM130423Postdoctoral FellowshipDE0309711008R00 DE030972K99 DE030972K99 DE030971DE13172DE023017F31 DE027860F31 DE023017R01 DE013172DE027860Swanson SSardiu MEMoore ELLi LDash SFitriasari SZhao RSakai DUnruh JAchilleos AShiang RWatt KENDixon MJTsuchiya DChilders MBugarinovic GTrainor PAFalcon KTDixon JfalseDynamic regulation and requirement for ribosomal RNA transcription during mammalian development.Ribosomal RNA (rRNA) transcription by RNA polymerase I (Pol I) is a critical rate-limiting step in ribosome biogenesis, which is essential for cell survival. Despite its global function, disruptions in ribosome biogenesis cause tissue-specific birth defects called ribosomopathies, which frequently affect craniofacial development. Here, we describe a cellular and molecular mechanism underlying the susceptibility of craniofacial development to disruptions in Pol I transcription. We show that Pol I subunits are highly expressed in the neuroepithelium and neural crest cells (NCCs), which generate most of the craniofacial skeleton. High expression of Pol I subunits sustains elevated rRNA transcription in NCC progenitors, which supports their high tissue-specific levels of protein translation, b2022-01-01T00:00:00Z2022 Aug2025-04-19T13:33:11.623Z2025-04-19T13:33:11.623ZS-EPMC93513563588179210.1073/pnas.2116974119