Osteoblasts pattern endothelium and somatosensory axons during zebrafish caudal fin organogenesis

Abstract

Skeletal elements frequently associate with vasculature and somatosensory nerves, which regulate bone development and homeostasis. However, the deep, internal location of bones in many vertebrates has limited in vivo exploration of the neurovascular-bone relationship. Here, we use the zebrafish caudal fin, an optically accessible organ formed of repeating bony ray skeletal units, to determine the cellular relationship between nerves, bones, and endothelium. In adults, we establish the presence of somatosensory axons running through the inside of the bony fin rays, juxtaposed with osteoblasts on the inner hemiray surface. During development, we show the caudal fin progresses through sequential stages of endothelial plexus formation, bony ray addition, ray innervation, and endothelial remodeling. Surprisingly, the initial stages of fin morphogenesis proceed normally in animals lacking either fin endothelium or somatosensory nerves. Instead, we find that sp7+ osteoblasts are required for endothelial remodeling and somatosensory axon innervation in the developing fin. Overall, this study demonstrates that the proximal neurovascular-bone relationship in the adult caudal fin is established during fin organogenesis, and suggests that ray-associated osteoblasts pattern axons and endothelium.

Temporally and regionally distinct morphogenetic processes govern zebrafish tail fin blood vessel network expansion

“…Previous studies have shown that specialized vascular beds exist within distinct organs and that blood vessels can also direct organ development (Gomez-Salinero et al, 2021;Lammert et al, 2001;Rafii et al, 2016;Stenman et al, 2008). Blood vessels furthermore align with anatomical structures, such as bones and nerves (Bump et al, 2022;Larrivee et al, 2009). Previous studies identified hard-wired genetic mechanisms that lead to the formation of a stereotyped vasculature, for example within the trunk of the zebrafish embryo (Childs et al, 2002;Hogan and Schulte-Merker, 2017;Isogai et al, 2001;Siekmann and Lawson, 2007), the hindbrain (Bussmann et al, 2011;Fujita et al, 2011), or the pectoral fins (Paulissen et al, 2022).…”

“…The formation of this plexus further depends on structural features of the extracellular matrix, as interfering with collagen assembly results in plexus defects (Huang et al, 2003;Huang et al, 2009;Nakagawa et al, 2022;Senk and Djonov, 2021). A recent report showed that osteoblasts are required for normal fin blood vessel outgrowth (Bump et al, 2022). This indicates that osteoblasts likely secrete pro-angiogenic factors, as also proposed by Paulissen et al (Paulissen et al, 2022).…”

“…Fin blood vessel formation requires Vascular Endothelial Growth Factor (VEGF) signalling (Bayliss et al, 2006;Bump et al, 2022). Fins lacking blood vessels did not show overt patterning defects in bone or nerve fibres but failed to grow after the initial stages of morphogenesis (Bump et al, 2022). This was more pronounced during fin regeneration (Bayliss et al, 2006).…”

Coordinated patterning of zebrafish caudal fin symmetry by a central and two peripheral organizers

“…In addition, the HDOC may also influence the branching of the caudal vasculature and caudal nerve axons that each ramify dorsally and ventrally at the hypural diastema. 4,6,35 Together, the HDOC likely broadly patterns the surrounding mesoderm and its innervating axons.…”

“…[43][44][45] Similar to the observed muscle-to-ray set pairings, PPRs and CPRs show distinct innervation. 35 Together, the different ontogeny of PPRs and CPRs under the control of three organizing centers may provide each ray set with distinct identities altering ray morphology as well as muscle and nerve targeting, collectively optimizing biomechanical properties for efficient thrust and maneuverability.…”