Biology subjects

Ishimatsu, K.

Publications and source records attributed to Ishimatsu, K..

3 recordsLinked to original sources

bioRxiv2025

A single-cell transcriptomic atlas of inner ear morphogenesis in zebrafish

The inner ear constitutes different cell types next to one another: the sensory patches whose hair cells synapse with neurons, the thin channels of three semicircular canals whose perpendicular organization enables detection of directional head rotation, and the endolymphatic duct and sac whose conditional epithelial barrier relieves excess pressure and promotes fluid pressure homeostasis. How the ears component cell states are established during development has remained unknown. We use single-cell RNA sequencing to distinguish cell states within the developing ear with wild-type zebrafish embryos and lmx1bb mutants that exhibit defects in canal and sac morphogenesis. We identify the earliest marker for the semicircular canal-genesis zone (ccn1l1), unexpected genes in the endolymphatic sac that suggest a role for tissue contraction in its function (smtnb), parallel gene sets for sensory patches in the neuromast and ear, and a conserved role for cell-cycle pausing (cdkn1bb expression in the canals and sac as previously observed in the developing mouse ear). This atlas provides the most comprehensive transcriptional profiling of the developing inner ear, identifying new molecular leads to understand ear morphogenesis. Summary statementSingle-cell transcriptomic analysis of developing wild-type and lmx1bb mutant zebrafish reveals cell-states and effectors that distinguish the inner ears sensory patches, semicircular canals, endolymphatic duct and sac, and periotic mesenchyme.

developmental biology↗

bioRxiv2018

A Scube2-Shh feedback loop links morphogen release to morphogen signaling to enable scale invariant patterning of the ventral neural tube

To enable robust patterning, morphogen systems should be resistant to variations in gene expression and tissue size. Here we explore how the Sonic Hedgehog (Shh) morphogen gradient in the ventral neural tube enables scaled patterning in embryos of varying sizes. Using zebrafish eggs that have been surgically reduced in size, we find that ventral neural tube patterning remains proportional in smaller embryos. Intriguingly, a secreted protein implicated in Shh release, Scube2, is expressed in the dorsal-intermediate neural tube far from Shh producing cells. Overexpression of scube2 expands the Shh gradient whereas loss of scube2 causes gradient contraction. Conversely, upregulation of Shh represses scube2 expression while Shh downregulation increases scube2 expression thus establishing a negative feedback loop. This regulatory feedback is necessary for scaling, as demonstrated by its loss in scube2 overexpressing embryos. Using mathematical modeling, we show that feedback control on diffusion and release rates of Shh allows the morphogen gradient to be robust to differences in field length and Shh gene dosage. We conclude that Scube2 promotes release and diffusion of Shh to allow gradient scaling in an extension to the expander-repressor model. Summary StatementThe Shh morphogen gradient can scale to different size tissues by feedback between Scube2 mediated release and diffusion of Shh and Shh based inhibition of Scube2 expression

developmental biology↗

bioRxiv2017

Size-reduced embryos reveal a gradient scaling based mechanism for zebrafish somite formation

Little is known about how the sizes of animal tissues are controlled. A prominent example is somite size which varies widely both within an individual and across species. Despite intense study of the segmentation clock governing the timing of somite generation, how it relates to somite size is poorly understood. Here we examine somite scaling and find that somite size at specification scales with the length of the presomitic mesoderm (PSM) despite considerable variation in PSM length across developmental stages and in surgically size-reduced embryos. Measurement of clock period, axis elongation speed, and clock gene expression patterns demonstrate that existing models fail to explain scaling. We posit a \"clock and scaled gradient\" model, in which somite boundaries are set by a dynamically scaling signaling gradient across the PSM. Our model not only explains existing data, but also makes a unique prediction that we experimentally confirm--the formation of periodic \"echoes\" in somite size following perturbation of the size of one somite. Our findings demonstrate that gradient scaling plays a central role both in progression and size control of somitogenesis.\n\nSummary statementBy comparing patterning in zebrafish embryos of different size we show that a dynamically scaling gradient in the presomitic mesoderm regulates somite size control.

developmental biology↗