Recovery of shape and size in a developing organ pair

Abstract

Background 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. Results 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. Conclusions 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.

Dilp8 controls a time window for tissue size adjustment inDrosophila

“…5b) Unexpectedly, we find that discs adjust their volume through a major adjustment step taking place immediately after the L/P transition. This contrasts with recent descriptions made in zebra fish where symmetrically developing inner ears and somites adjust progressively over time 20,21 . We show that the relaxin-like Dilp8 is required for a major adjustment step taking place after WPP.…”

Size control of the inner ear via hydraulic feedback

“…Interestingly, analysis of the system of equations in our model shows that the vesicle will adjust endolymph flux to account for perturbations to vesicle size, via a mechanical feedback loop that links pressure to flux (Figure 3J). Such a control system could be useful to correct natural as well as experimentally induced asymmetry across the left-right axis as we have found in early zebrafish inner ear development (Green et al, 2017), and in the whole mammalian embryo (Chan et al, 2019).…”

“…Catch-up growth also occurs in vertebrates: if an infant heart or kidney is transplanted into an adult, it grows faster than the surrounding tissue to catch-up to a target size (Dittmer et al, 1974; Silber, 1976). Recently, the related phenomenon of organ symmetry has been addressed in the context of tails and the inner ear; but, the control mechanism underlying catch-growth was not clearly identified (Das et al, 2017; Green et al, 2017). Catch-up growth also occurs during bone growth and its study has clarified insulin signaling activity as being important for bone size control (Roselló-Díez and Joyner, 2015; Roselló-Díez et al, 2017; Roselló-Díez et al, 2018).…”

Fish size effect on sagittal otolith outer shape variability in round gobyNeogobius melanostomus(Pallas 1814)

“…In bilaterally symmetrical roundfishes, symmetry is expected to be the rule and to be maintained by homeostasis processes (Palmer, 2009). The origin and consequences of otolith FA on fish remain largely unknown, but it is regularly associated with stress and/or environmental heterogeneity; thus, it is thought to be an indicator of developmental instability and could be considered a sensitive indicator of fish health that directly affects fish performance because otoliths are essential to balance and hearing (Díaz‐Gil et al ., 2015; Green et al ., 2017; Lemberget & McCormick, 2009). Otolith shape asymmetry is linked to kinetotic swimming in fish, and it can generate some dysfunction in vestibular sensing that also affects acoustic functionality (Hilbig et al ., 2011; Lychakov et al ., 2008).…”