Green Amelia A, Mosaliganti Kishore R, Swinburne Ian A, Obholzer Nikolaus D, Megason Sean G
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts.
Dev Dyn. 2017 Jun;246(6):451-465. doi: 10.1002/dvdy.24498. Epub 2017 Apr 3.
Paired organs in animals are largely bilaterally symmetric despite inherent noise in most biological processes. How is precise organ shape and size achieved during development despite this noise? Examining paired organ development is a challenge because it requires repeated quantification of two structures in parallel within living embryos. Here we combine bilateral quantification of morphology through time with asymmetric perturbations to study regulation of organ shape, size, and symmetry in developing organ pairs.
We present quantitative live imaging tools to measure the shape and size of the developing inner ears on both the left and right side simultaneously over time. By quantifying variation between the left and right inner ear (intrinsic noise) and between different individuals (extrinsic noise), we find that initial variability decreases over time in normal development to achieve symmetry. Early asymmetry is increased by environmental stress, but symmetry is still recovered over subsequent developmental time. Using multiple unilateral perturbations including Fgf signaling and ultraviolet light, we find that growth can be adjusted to compensate for a range of initial size and shape differences.
We propose that symmetry in developmental systems does not emerge through precise deterministic bilateral development, but rather through feedback mechanisms that adjust morphogenesis rates to account for variation. Developmental Dynamics 246:451-465, 2016. © 2017 Wiley Periodicals, Inc.
尽管大多数生物过程中存在内在噪声,但动物体内的成对器官在很大程度上是双侧对称的。尽管存在这种噪声,在发育过程中如何实现精确的器官形状和大小呢?研究成对器官的发育是一项挑战,因为它需要在活体胚胎中对两个结构同时进行反复定量分析。在这里,我们将随时间对形态的双侧定量分析与不对称扰动相结合,以研究发育中的成对器官的形状、大小和对称性的调控机制。
我们展示了定量实时成像工具,可随时间同时测量发育中的内耳左右两侧的形状和大小。通过量化左右内耳之间的差异(内在噪声)以及不同个体之间的差异(外在噪声),我们发现正常发育过程中初始变异性会随时间降低以实现对称性。环境压力会增加早期不对称性,但在随后的发育过程中对称性仍会恢复。使用包括Fgf信号传导和紫外线在内的多种单侧扰动,我们发现生长可以进行调整以补偿一系列初始大小和形状差异。
我们提出,发育系统中的对称性并非通过精确的确定性双侧发育形成,而是通过反馈机制来调整形态发生速率以应对变异而形成。《发育动力学》246:451 - 465,2016年。©2017威利期刊公司。