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Series GSE151354 Query DataSets for GSE151354
Status Public on Jan 16, 2021
Title Single cell analysis of juvenile Nkx3.2 mutant zebrafish craniofacial skeleton
Organism Danio rerio
Experiment type Expression profiling by high throughput sequencing
Summary The specification and maintenance of distinct zones of chondrocytes within growth plates and joints ensures proper skeletal development through adulthood. Rare mutations in the transcription factor NKX3.2 underlie Spondylo-megaepiphyseal-metaphyseal dysplasia (SMMD), which is characterized by skeletal defects including scoliosis, large epiphyses, wide growth plates, and supernumerary joints in the distal limbs. Embryonic knockdown of nkx3.2 function in zebrafish had revealed a requirement in jaw joint specification, yet embryonic lethality of nkx3.2 knockdown zebrafish and mouse Nkx3.2 mutants had precluded an analysis of post-embryonic functions. Here we report adult viable nkx3.2 zebrafish mutants that display ectopic cartilage overgrowth in place of a missing jaw joint, as well as severe dysmorphologies of the facial skeleton, skullcap, and spine. We also isolate rare viable nkx3.2 knockdown animals that lack the jaw joint but fail to display ectopic cartilage growth and scoliosis, indicating post-embryonic roles for Nkx3.2 beyond jaw joint specification. Consistently, we observe nkx3.2 expression in the subarticular zone of the adult jaw joint and in pre-hypertrophic growth plate chondrocytes. Single-cell RNA sequencing reveals an upregulation of stress-induced pathways in mutants, including the prostaglandin D2 synthase ptgdsb.1 and the mTOR regulator sestrin1, which we confirm by in situ RNA analysis of the defective jaw joint region. Our data reveal a zebrafish model for the joint and spine defects of SMMD and point to post-embryonic roles for Nkx3.2 in buffering the stress response and dampening proliferation in joint-adjacent chondrocytes.
Overall design Single cell RNA sequencing of FACS isolated cartilages (fli:GFP/sox10:DsRed+) from wildtype and nkx3.2 mutants
Contributor(s) Smeeton J, Crump G
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Submission date May 28, 2020
Last update date Jan 18, 2021
Contact name Joanna Smeeton
Organization name Columbia University Irving Medical Center
Department Rehabilitation and Regenerative Medicine
Lab Smeeton Lab
Street address 650 W 168TH ST, ROOM 1110, William Black Building
City New York
State/province NY
ZIP/Postal code 10032
Country USA
Platforms (1)
GPL20828 Illumina NextSeq 500 (Danio rerio)
Samples (2)
GSM4575942 WT cartilage
GSM4575943 nkx3.2 mutant cartilage
BioProject PRJNA635584
SRA SRP265073

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Supplementary file Size Download File type/resource
GSE151354_RAW.tar 15.1 Mb (http)(custom) TAR (of MTX, TSV)
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Raw data are available in SRA
Processed data provided as supplementary file

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