RRC ID 51573
著者 Garcia J, Bagwell J, Njaine B, Norman J, Levic DS, Wopat S, Miller SE, Liu X, Locasale JW, Stainier DYR, Bagnat M.
タイトル Sheath Cell Invasion and Trans-differentiation Repair Mechanical Damage Caused by Loss of Caveolae in the Zebrafish Notochord.
ジャーナル Curr Biol
Abstract The notochord, a conserved axial structure required for embryonic axis elongation and spine development, consists of giant vacuolated cells surrounded by an epithelial sheath [1-3]. During morphogenesis, vacuolated cells maintain their structural integrity despite being under constant mechanical stress [4]. We hypothesized that the high density of caveolae present in vacuolated cells [5, 6] could buffer mechanical tension. Caveolae are 50- to 80-nm membrane invaginations lined by cage-like polygonal structures [7, 8] formed by caveolin 1 (Cav1) or Cav3 and one of the cavin proteins [6, 9-11]. Recent in vitro work has shown that plasma membrane caveolae constitute a membrane reservoir that can buffer mechanical stresses such as stretching or osmotic swelling [12]. Moreover, mechanical integrity of vascular and muscle cells is partly dependent on caveolae [13-15]. However, the in vivo mechano-protective roles of caveolae have only begun to be explored. Using zebrafish mutants for cav1, cav3, and cavin1b, we show that caveolae are essential for notochord integrity. Upon loss of caveola function, vacuolated cells collapse at discrete positions under the mechanical strain of locomotion. Then, sheath cells invade the inner notochord and differentiate into vacuolated cells, thereby restoring notochord function and allowing normal spine development. Our data further indicate that nucleotides released by dying vacuolated cells promote sheath cell vacuolization and trans-differentiation. This work reveals a novel structural role for caveolae in vertebrates and provides unique insights into the mechanisms that safeguard notochord and spine development.
巻・号 27(13)
ページ 1982-1989.e3
公開日 2017-7-10
DOI 10.1016/j.cub.2017.05.035
PII S0960-9822(17)30571-7
PMID 28648824
PMC PMC5526084
MeSH Animals Biomechanical Phenomena Caveolae / metabolism* Cell Differentiation Mutation Notochord / embryology* Stress, Mechanical Zebrafish / embryology* Zebrafish / genetics
IF 9.601
引用数 26
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