a spatial and temporal gradient of fgf differentially regulates distinct stages of neural development in the zebrafish inner earfgf的时空梯度差异调节斑马鱼神经发育的不同阶段内耳.pdfVIP
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a spatial and temporal gradient of fgf differentially regulates distinct stages of neural development in the zebrafish inner earfgf的时空梯度差异调节斑马鱼神经发育的不同阶段内耳
A Spatial and Temporal Gradient of Fgf Differentially
Regulates Distinct Stages of Neural Development in the
Zebrafish Inner Ear
Shruti Vemaraju, Husniye Kantarci, Mahesh S. Padanad, Bruce B. Riley*
Biology Department, Texas AM University, College Station, Texas, United States of America
Abstract
Neuroblasts of the statoacoustic ganglion (SAG) initially form in the floor of the otic vesicle during a relatively brief
developmental window. They soon delaminate and undergo a protracted phase of proliferation and migration (transit-
amplification). Neuroblasts eventually differentiate and extend processes bi-directionally to synapse with hair cells in the
inner ear and various targets in the hindbrain. Our studies in zebrafish have shown that Fgf signaling controls multiple
phases of this complex developmental process. Moderate levels of Fgf in a gradient emanating from the nascent utricular
macula specify SAG neuroblasts in laterally adjacent otic epithelium. At a later stage, differentiating SAG neurons express
Fgf5, which serves two functions: First, as SAG neurons accumulate, increasing levels of Fgf exceed an upper threshold that
terminates the initial phase of neuroblast specification. Second, elevated Fgf delays differentiation of transit-amplifying cells,
balancing the rate of progenitor renewal with neuronal differentiation. Laser-ablation of mature SAG neurons abolishes
feedback-inhibition and causes precocious neuronal differentiation. Similar effects are obtained by Fgf5-knockdown or
global impairment of Fgf signaling, whereas Fgf misexpression has the opposite effect. Thus Fgf signaling renders SAG
development self-regulating, ensuring steady production of an appropriate number of neurons as the larva grows.
Citation: Vemaraju S, Kantarci H, Padanad MS, Riley BB (2012) A
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