First person – Sabrina Alam

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First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Sabrina Alam is first author on ‘ Snrpb is required in murine neural crest cells for proper splicing of genes essential for craniofacial morphogenesis ’, published in DMM. Sabrina is a PhD student in the lab of Dr Loydie A. Jerome-Majewska at McGill University, Montreal, Canada, investigating the role of splicing in the complexity of craniofacial development.

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Snrpb is required in murine neural crest cells for proper splicing and craniofacial morphogenesis

Sabrina Alam, Shruti Kumar, Marie-Claude Beauchamp … (2022)

Heterozygous mutations in SNRPB , an essential core component of the five small ribonucleoprotein particles of the spliceosome, are responsible for cerebrocostomandibular syndrome (CCMS). We show that Snrpb heterozygous mouse embryos arrest shortly after implantation. Additionally, heterozygous deletion of Snrpb in the developing brain and neural crest cells models craniofacial malformations found in CCMS, and results in death shortly after birth. RNAseq analysis of mutant heads prior to morphological defects revealed increased exon skipping and intron retention in association with increased 5′ splice site strength. We found increased exon skipping in negative regulators of the P53 pathway, along with increased levels of nuclear P53 and P53 target genes. However, removing Trp53 in Snrpb heterozygous mutant neural crest cells did not completely rescue craniofacial development. We also found a small but significant increase in exon skipping of several transcripts required for head and midface development, including Smad2 and Rere . Furthermore, mutant embryos exhibited ectopic or missing expression of Fgf8 and Shh , which are required to coordinate face and brain development. Thus, we propose that mis-splicing of transcripts that regulate P53 activity and craniofacial-specific genes contributes to craniofacial malformations. This article has an associated First Person interview with the first author of the paper. Summary: We report the first mouse model for cerebrocostomandibular syndrome, showing that mis-splicing of transcripts that regulate P53 activity and craniofacial-specific genes contributes to craniofacial malformations.

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Journal ID (nlm-ta): Dis Model Mech

Journal ID (iso-abbrev): Dis Model Mech

Journal ID (publisher-id): DMM

Journal ID (hwp): dmm

Title: Disease Models & Mechanisms

Publisher: The Company of Biologists Ltd

ISSN (Print): 1754-8403

ISSN (Electronic): 1754-8411

Publication date Collection: 1 June 2022

Publication date (Electronic): 23 June 2022

Publication date PMC-release: 23 June 2022

Volume: 15

Issue: 6

Electronic Location Identifier: dmm049668

Article

Publisher ID: DMM049668

DOI: 10.1242/dmm.049668

PMC ID: 9235874

SO-VID: f832a07c-1787-4122-acdd-bd8030cdc437

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This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

First person – Sabrina Alam

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Snrpb is required in murine neural crest cells for proper splicing and craniofacial morphogenesis

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