Extended Data Fig. 1: A putative gene regulatory network (GRN) underlying the dual structural novelties of the human ilium.

a, In EARLY-stage non-human primates (NHP) and mice, the ilium (cartilage in blue) is oriented longitudinally (top), with resting zone (RZ) marker UCMA and early proliferating marker PTH1R positioned at the cranial end, while SOX9, an early chondrocyte marker, is expressed throughout the cranio-caudal ilium (bottom, section). In the EARLY-stage human ilium, the anteroposterior (AP) axis which is initially rod-like, widens while the vertical axis shortens (top). In cross-section, SOX9 is expressed bilaterally along the AP axis, followed by PTH1R, which gets restricted to the anterior pole. ZNF521, located external to undifferentiated chondrocytes, interacts with PTH1R (bottom, section). In LATE-stage NHPs and mice, ilium ossification (white) initiates at mid-length and extends along the longitudinal axis (top); UCMA (RZ marker) is present at cranial and caudal ends, with PTH1R positioned between the hypertrophic zone (HZ, marked by COL10A1) and the RZ. RUNX2, an osteoblast marker, is expressed internally and along the perichondrium (Pe) at ossification sites in mice and NHPs (bottom). In LATE-stage human ilium, ossification initiates posteriorly and extends radially (top; white arrows); COMP, PTH1R, COL10A1 are expressed along the transversely oriented growth plate, while RUNX2 is expressed along the perichondrium, illustrating delayed internal ossification (bottom). Cartoon schematics of human, chimpanzee, mouse and, mouse lemur were created in BioRender. Senevirathne, G. (2025) https://BioRender.com/p7qcwtp. b, Ossification extends radially, and several muscles (red), including the three gluteal muscles (maximus posterior, medius intermediate, and minimus anterior) and the rectus femoris (RF), attach to the ilium early in development. c. A summary of the interactive network underlying these developmental shifts (see text). Additional abbreviations: ASIS, anterior superior iliac spine; AIIS, anterior inferior iliac spine; IL, ilium; FM, femur.