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Geminin is required for Hox gene regulation to pattern the developing limb
- Source :
- Dev Biol
- Publication Year :
- 2020
-
Abstract
- 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 elaboration of distinct limb skeletal elements. 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 the 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.SummaryThis work identifies a new role for Geminin in mouse limb development. Geminin is a nuclear protein that regulates gene expression to control several other aspects of vertebrate development.
- Subjects :
- animal structures
Mice, Transgenic
Hindlimb
Article
03 medical and health sciences
Limb bud
Mice
0302 clinical medicine
GLI3
medicine
Limb development
Animals
Hedgehog Proteins
Hox gene
Molecular Biology
Transcription factor
030304 developmental biology
Regulation of gene expression
Homeodomain Proteins
0303 health sciences
biology
030302 biochemistry & molecular biology
Geminin
Gene Expression Regulation, Developmental
Cell Biology
Embryo, Mammalian
Cell biology
body regions
Patched-1 Receptor
medicine.anatomical_structure
embryonic structures
biology.protein
Forelimb
030217 neurology & neurosurgery
Developmental Biology
Transcription Factors
Subjects
Details
- ISSN :
- 1095564X
- Volume :
- 464
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Developmental biology
- Accession number :
- edsair.doi.dedup.....c6ca1c2e7c446d7bd3b9cf59c75e039d