Single-cell profiling of penta- and tetradactyl mouse limb buds identifies mesenchymal progenitors controlling digit numbers and identities
Single-cell profiling of penta- and tetradactyl mouse limb buds identifies mesenchymal progenitors controlling digit numbers and identities
SUMMARY The cellular mechanisms controlling digit numbers and identities have remained elusive. Profiling of wild-type (pentadactyl) and Grem1 tetradactyl mouse limb buds identifies cellular changes affecting two limb bud mesenchymal progenitor (LMP) populations. In mutant limb buds, the anteriorly biased distribution of peripheral LMPs (pLMPs) is lost and the population expanded, while the distal-posterior LMP (dLMP) population is reduced from early stages onward. Analysis of LMP signature genes in wildtype and mutant mouse limb buds with digit loss or gain establishes that pLMPs are positively regulated by BMP signaling, while dLMPs require GREM1-mediated BMP antagonism. dLMPs encompass digit progenitors and altering their population size prefigures changes in digit numbers. The anteriorly biased pLMP distribution is linked to digit asymmetry as loss of this bias in tetradactyl mouse and pig limb buds underlies middle digit symmetry and identity loss. This study indicates that variable spatial Grem1 expression in mutant and evolutionary diversified limb buds tunes BMP activity, impacting both LMP populations in a complementary manner.
Palacio Victorio、Pancho Anna、Zeller Rolf、Treutlein Barbara、Morabito Angela、Zuniga Aim¨|e、Malkmus Jonas、He Zhisong、Soussi Geoffrey
Developmental Genetics, Department Biomedicine, University of BaselDevelopmental Genetics, Department Biomedicine, University of BaselDevelopmental Genetics, Department Biomedicine, University of BaselQuantitative Developmental Biology Lab, Department of Biosystems Science and EngineeringDevelopmental Genetics, Department Biomedicine, University of BaselDevelopmental Genetics, Department Biomedicine, University of BaselDevelopmental Genetics, Department Biomedicine, University of BaselQuantitative Developmental Biology Lab, Department of Biosystems Science and EngineeringDevelopmental Genetics, Department Biomedicine, University of Basel
细胞生物学遗传学分子生物学
Gremlin1BMP antagonismTfap2blimb bud mesenchymal progenitorsmousepig limb bud developmentdigit specificationsingle-cell RNA sequencingpentadactylytetradactyly
Palacio Victorio,Pancho Anna,Zeller Rolf,Treutlein Barbara,Morabito Angela,Zuniga Aim¨|e,Malkmus Jonas,He Zhisong,Soussi Geoffrey.Single-cell profiling of penta- and tetradactyl mouse limb buds identifies mesenchymal progenitors controlling digit numbers and identities[EB/OL].(2025-03-28)[2025-05-28].https://www.biorxiv.org/content/10.1101/2024.06.03.597099.点此复制
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