The PNS inhibits β₃-adrenergic–dependent BM egress of HSPCs at night. HSPCs, measured as CFU-Cs (A), and WBCs (B) circulating at ZT13, 16 weeks after BM transplantation into lethally irradiated mice. Gfra2^−/− mice and control Gfra2^+/− mice were used as donor (lower genotypes) or recipients (upper genotypes) in all combinations. (C) Cxcl12 mRNA expression in the BM of Gfra2^−/− and Gfra2^+/− control mice at the specified ZT. ZT21 has been duplicated to facilitate viewing. (D) Cxcl12 concentration in BM extracellular fluid (BMECF) at ZT13. (E) Kitl mRNA expression in the BM of Gfra2^−/− and Gfra2^+/− control mice at ZT13. (F) Number of stromal Nes-GFP^hi/lo cells in endosteal and nonendosteal BM (upper panel). Representative flow cytometry plot showing CD31 and Nes-GFP expression in CD45⁻Ter119⁻ cells isolated from endosteal BM of Gfra2^−/− and control Gfra2^+/+ mice (lower panel). (G) CFU-C fold change at ZT13 in control Gfra2^+/− mice, Gfra2^−/− mice, single β₂- or β₃-AR (Adrb2, Adrb3)–deficient mice, or compound Gfra2^−/−Adrb2^−/− and Gfra2^−/−Adrb3^−/− mice. (H) WBCs circulating at ZT13 in control Gfra2^+/− mice, Gfra2^−/− mice, single β₂- or β₃-AR (Adrb2, Adrb3)–deficient mice, or compound Gfra2^−/−Adrb2^−/− and Gfra2^−/−Adrb3^−/− mice. All data are mean ± standard error of the mean; n (inside bars) and P values (multivariate analysis for >2 groups) are indicated. *P < .05, **P < .01, ***P < .001, 1-way analysis of variance with Bonferroni comparisons (A-B,F-H), multiple 2-tailed test (C), unpaired 2-tailed t test (D-E). ns, not significant.