Jagged-Notch Signaling is Involved in Zebrafish Notochord Development

Mai Yamamoto1, Kunihiro Matsumoto1, Shigenobu Yonemura2, Koichi Kawakami3, Motoyuki Itoh1

1) Nagoya University, Nagoya, Japan, 2) RIKEN CDB, Kobe, Japan,3)NIG, Mishima, Japan

  The notochord is an early midline structure of mesodermal origin. As the notochord differentiates, a large vacuole is inflated within cells and the peri-notochordal basement membrane is formed. This structure development is important for the notochord to serves as the axial skeleton. Many studies have revealed its early patterning roles. However the mechanism by which the notochord structure is formed and maintained is not fully understood.
  The Notch signaling pathway plays an important role in the determination of cell fate/differentiation in a number of organs. We found inhibition of Jagged-Notch signaling led to morphological defects of the notochord. In Notch signaling deficient embryos such as mind bomb mutants, jagged1a /1b or su(H) morphants, the notochord cells became vacuolated but were more spherical instead of rod-like shape. Time- lapse analysis revealed notochord cells differentiated into two types of cells, vacuolated and non-vacuolated cells. We found that the number of vacuolated cell was increased, but non-vacuolated cells were decreased in Jagged-Notch signaling deficient embryos. We also found type II collagen protein in the peri-notochordal basement membrane was decreased in Jagged-Notch signaling deficient embryos. This observation is consistent with the reduction of non-vacuolated cells because the production of type II collagen mainly depends on non-vacuolated cells but not on vacuolated cells. Furthermore notochord cell specific activation of notch by GAL4UAS system resulted in ectopic collagen production and reduction of vacuolated cells. Thus, our data suggest Jagged-Notch signaling controls commitment to a non-vacuolated cell fate to enable peri-notochordal basement formation required for notochord structural integrity.