AI Article Synopsis
- The study explores how G protein-coupled receptor Gpr161, located in primary cilia, affects tissue development by regulating the hedgehog signaling pathway through cAMP.
- In engineered mice with a version of Gpr161 that lacks ciliary localization but retains cAMP signaling, researchers observed delayed embryonic death and changes in Gli transcription factors responsible for growth and differentiation.
- The findings suggest that both ciliary and extraciliary Gpr161 are crucial in setting Gli repressor levels, influencing morphogenetic traits like limb and facial structure development.
Article Abstract
The role of compartmentalized signaling in primary cilia during tissue morphogenesis is not well understood. The cilia localized G protein-coupled receptor, Gpr161, represses hedgehog pathway via cAMP signaling. We engineered a knock-in at the locus in mice to generate a variant (Gpr161), which was ciliary localization defective but cAMP signaling competent. Tissue phenotypes from hedgehog signaling depend on downstream bifunctional Gli transcriptional factors functioning as activators or repressors. Compared to knockout (ko), had delayed embryonic lethality, moderately increased hedgehog targets, and partially down-regulated Gli3 repressor. Unlike ko, the neural tube did not show Gli2 activator-dependent expansion of ventral-most progenitors. Instead, the intermediate neural tube showed progenitor expansion that depends on loss of Gli3 repressor. Increased extraciliary receptor levels in prevented ventralization. Morphogenesis in limb buds and midface requires Gli repressor; these tissues in manifested hedgehog hyperactivation phenotypes-polydactyly and midfacial widening. Thus, ciliary and extraciliary Gpr161 pools likely establish tissue-specific Gli repressor thresholds in determining morpho-phenotypic outcomes.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378848 | PMC |
| http://dx.doi.org/10.7554/eLife.67121 | DOI Listing |
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