Hox5 Genes Regulate the Wnt2/2b-Bmp4-Signaling Axis during Lung Development
| Autor: | Nicholas C. Baker, Steven M. Hrycaj, Briana R. Dye, Brian M. Larsen, Ann C. Burke, Deneen M. Wellik, Jason R. Spence |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Mesoderm
animal structures Mesenchyme Organogenesis Bone Morphogenetic Protein 4 Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Mice 0302 clinical medicine SOX2 WNT2 medicine AXIN2 Animals Hox gene Lung lcsh:QH301-705.5 030304 developmental biology Homeodomain Proteins 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction Gene Expression Regulation Developmental Molecular biology Mice Mutant Strains Cell biology Crosstalk (biology) medicine.anatomical_structure Bone morphogenetic protein 4 lcsh:Biology (General) embryonic structures 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Cell Reports, Vol 12, Iss 6, Pp 903-912 (2015) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2015.07.020 |
| Popis: | SummaryHox genes are required for proper anteroposterior axial patterning and the development of several organ systems. Here, we show that all three Hox5 paralogous genes play redundant roles in the developing lung. Hoxa5;Hoxb5;Hoxc5 triple-mutant embryos develop severely hypoplastic lungs with reduced branching and proximal-distal patterning defects. Hox5 genes are exclusively expressed in the lung mesoderm; however, defects are observed in both lung mesenchyme and endodermally derived epithelium, demonstrating that Hox5 genes act to regulate mesodermal-epithelial crosstalk during development. We show that Hox5 loss of function leads to loss of Wnt2/2b expression in the distal lung mesenchyme and the downregulation of previously identified downstream targets of Wnt2/2b signaling, including Lef1, Axin2, and Bmp4. Wnt2/2b-enriched media rescue proper Sox2/Sox9 patterning and restore Bmp4 expression in Hox5 triple-mutant lung explants. Taken together, these data show that Hox5 genes are key upstream mesenchymal regulators of the Wnt2/2b-Bmp4-signaling axis critical for proper lung patterning. |
| Databáze: | OpenAIRE |
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