VEGFR1 increases MK migration to vascular niche via a CXCR4-dependent process. Mice were administered either VEGF-A₁₆₅, PlGF-2, VEGF-E (100 μg/kg intraperitoneally), or vehicle (PBS) each day for 4 consecutive days before bone marrow and spleens were harvested 24 hours later. (A) Percentage of CD41⁺ MKs expressing CXCR4. (B) Percentage of 2n-8n and ≥ 16n CD41⁺ MKs expressing CXCR4 in bone marrow and spleen. Other groups of mice were administered a CXCR4 antagonist (AMD3100 5 mg/kg) or PBS b.i.d. (bis in die: twice-daily dosing) for the 4 days of VEGF-A₁₆₅ treatment for evaluation of MK ploidy content. (C) Bone marrow MKs analyzed for ploidy content using TOPRO-3 24 hours after the last VEGF-A₁₆₅ injection. (D) Histogram revealing spread of bone marrow MK ploidy above 16n; n = 5-6 animals per group. Data are expressed as mean ± SEM; *P < .05, **P < .01, and ***P < .001 compared with control or as indicated.