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Series GSE143211 Query DataSets for GSE143211
Status Public on Jun 05, 2020
Title Geminin is required for Hox gene regulation to pattern the developing limb
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Development of the complex structure of the vertebrate limb requires carefully orchestrated interactions between multiple regulatory pathways and proteins. Among these, precise regulation of 5’ Hox transcription factor expression is essential for proper limb bud patterning and development. Here, we identified Geminin (Gmnn) as a novel regulator of this process. A conditional model of Gmnn deficiency resulted in loss or severe reduction of forelimb skeletal elements, while both the forelimb autopod and hindlimb were unaffected. 5’ Hox gene expression expanded into more proximal and anterior regions of embryonic forelimb buds in this Gmnn-deficient model. A second conditional model of Gmnn deficiency instead caused a similar but less severe reduction of hindlimb skeletal elements and hindlimb polydactyly, while not affecting the forelimb. An ectopic posterior Shh signaling center was evident in the anterior hindlimb bud of Gmnn-deficient embryos in this model. This center ectopically expressed Hoxd13, the Hoxd13 target Shh, and the Shh target Ptch1, while these mutant hindlimb buds also had reduced levels of the cleaved, repressor form of Gli3, a Shh pathway antagonist. Together, this work delineates a new role for Gmnn in modulating Hox expression to pattern the vertebrate limb.
Overall design Six litter and somite-matched pairs of Gmnnf/f; Prx-Cre (mutant) and Gmnn+/f; Prx-Cre (control) E10.5 embryos were used to prepare RNA. Batch correction was used to identify genes that were reproducibly differentially expressed genes (DEGs) across comparisons of paired mutant versus control samples.
Contributor(s) Lewis E, Sankar S, Tong C, Patterson E, Waller LE, Gontarz P, Zhang B, Ornitz D, Kroll KL
Citation(s) 32450229
Submission date Jan 06, 2020
Last update date Sep 07, 2020
Contact name Kristen L Kroll
Organization name Washington University School of Medicine
Department Developmental Biology
Lab Kristen Kroll
Street address 320 McDonnell Sciences/660 S. Euclid Ave.
City Saint Louis
State/province MO
ZIP/Postal code 63110
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (11)
GSM4252237 cont_litter_1452_m1
GSM4252238 cont_litter_1452_m3
GSM4252239 cont_litter_1425_m1
BioProject PRJNA599244
SRA SRP239651

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Supplementary file Size Download File type/resource
GSE143211_counts.txt.gz 2.9 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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