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Updated: Jun 21, 2026
A Method for Labeling Vasculature in Embryonic Mice
Published on: October 7, 2011
Vascular abnormalities and deregulation of VEGF in Lkb1-deficient mice
A Ylikorkala1, D J Rossi, N Korsisaari
1Molecular and Cancer Biology Program, Haartman Institute and Biomedicum Helsinki, Post Office Box 63, University of Helsinki, Helsinki 00014, Finland.
Abstract:
The LKB1 tumor suppressor gene, mutated in Peutz-Jeghers syndrome, encodes a serine/threonine kinase of unknown function. Here we show that mice with a targeted disruption of Lkb1 die at midgestation, with the embryos showing neural tube defects, mesenchymal cell death, and vascular abnormalities. Extraembryonic development was also severely affected; the mutant placentas exhibited defective labyrinth layer development and the fetal vessels failed to invade the placenta. These phenotypes were associated with tissue-specific deregulation of vascular endothelial growth factor (VEGF) expression, including a marked increase in the amount of VEGF messenger RNA. Moreover, VEGF production in cultured Lkb1(-/-) fibroblasts was elevated in both normoxic and hypoxic conditions. These findings place Lkb1 in the VEGF signaling pathway and suggest that the vascular defects accompanying Lkb1 loss are mediated at least in part by VEGF.
Insights
The LKB1 gene is crucial for embryonic development, regulating vascular endothelial growth factor (VEGF) signaling. Loss of LKB1 causes severe vascular defects and embryonic lethality, highlighting its role in angiogenesis.
Area of Science:
- Developmental biology
- Molecular genetics
- Cancer research
Background:
- The LKB1 gene, a tumor suppressor mutated in Peutz-Jeghers syndrome, encodes a serine/threonine kinase.
- The precise function of LKB1 in embryonic development and cellular processes remains largely unknown.
Purpose of the Study:
- To investigate the in vivo function of the LKB1 gene during embryonic development.
- To elucidate the molecular mechanisms underlying the developmental defects observed in Lkb1-deficient embryos.
Main Methods:
- Generation of Lkb1-deficient mice via targeted gene disruption.
- Phenotypic analysis of Lkb1 mutant embryos and extraembryonic tissues.
- Assessment of vascular endothelial growth factor (VEGF) expression and production in Lkb1-deficient cells.
Main Results:
- Targeted disruption of Lkb1 leads to embryonic lethality at midgestation.
- Lkb1 mutant embryos exhibit neural tube defects, mesenchymal cell death, and severe vascular abnormalities.
- Defects in placental development, including impaired labyrinth layer formation and fetal vessel invasion, were observed.
- Tissue-specific deregulation of VEGF expression, with increased VEGF mRNA levels, was associated with Lkb1 loss.
- Elevated VEGF production was detected in cultured Lkb1(-/-) fibroblasts under both normoxic and hypoxic conditions.
Conclusions:
- LKB1 plays a critical role in embryonic development, particularly in vascular formation and placental development.
- LKB1 is integrated into the VEGF signaling pathway.
- The vascular defects observed in Lkb1-deficient embryos are, at least in part, mediated by dysregulated VEGF signaling.
