|
| 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 |
| E-mail(s) |
kkroll@wustl.edu
|
| 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)
|
|
| Relations |
| BioProject |
PRJNA599244 |
| SRA |
SRP239651 |
Less...
More...