Grasses produce tiller and panicle branching at vegetative and reproductive stages; the branching patterns largely define the diversity of grasses and constitute a major determinant for grain yield of many cereals. Here we show that a spatiotemporally coordinated gene network consisting of the MicroRNA 156 (miR156/)miR529/ SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) and miR172/ APETALA2 (AP2) pathways regulates tiller and panicle branching in rice. SPL genes negatively control tillering, but positively regulate inflorescence meristem and spikelet transition. Underproduction or overproduction of SPLs reduces panicle branching, but by distinct mechanisms: miR156 and miR529 fine-tune the SPL levels for optimal panicle size. miR172 regulates spikelet transition by targeting AP2-like genes, which does not affect tillering, and the AP2-like proteins play the roles by interacting with TOPLESS-related proteins (TPRs). SPLs modulate panicle branching by directly regulating the miR172/ AP2 and PANICLE PHYTOMER2 (PAP2)/Rice TFL1/CEN homolog 1 (RCN1) pathways and also by integrating other regulators, most of which are not involved in tillering regulation. These findings may also have significant implications for understanding branching regulation of other grasses and for application in rice genetic improvement.he architecture of grasses is largely determined by the branching patterns. Tillers and inflorescence branches are produced at vegetative and reproductive stages, respectively, and their patterns greatly contribute to the diversity of grasses and constitute a major determinant of grain yield of major cereals.Rice branching has attracted much attention because of its importance in food production. Axillary buds produce tillers during the vegetative stage. However, only the early ones formed from the unelongated internodes outgrow as tillers, whereas later ones formed from the upper internodes remain dormant. After reproductive transition, the shoot apical meristem is converted to inflorescence meristem to produce panicle. Rice panicle morphology is largely determined by the timing of identity transition among the different types of meristems (SI Appendix, Fig. S1). Therefore, fine-tuning of meristem phase change at reproductive stage defines the size and architecture of the rice panicle (1).Many genes have been identified as regulators of rice branching. Generally, genes involved in axillary bud initiation control both vegetative and reproductive branching, whereas genes under axillary bud outgrowth have specific roles only at certain stages (2, 3). LAX PANICLE 1 (LAX1) and MONOCULM1 control axillary bud initiation; mutation in either of them results in reduction of both tiller and panicle branches (4, 5). Other genes such as Grain number, plant height, and heading date7 exclusively control panicle branching (6). As a third class, many genes, including Ideal Plant Architecture 1 (IPA1)/Wealthy Farmer's Panicle (WFP) and genes related to strigolactone, play opposite roles in tiller and panicle branches (7-9). Therefore...