bioRxiv Science⌕ Search

Biology subjects

Tsai, T. Y.-C.

Publications and source records attributed to Tsai, T. Y.-C..

2 recordsLinked to original sources

Neural plate pre-patterning enables specification of intermediate neural progenitors in the spinal cord

Spinal cord organization begins with the specification of a series of neural progenitor domains along the dorsal-ventral axis of the neural tube. Patterning at the dorsal and ventral ends is established by canonical morphogen gradients. Intermediate progenitor domains are located distally to morphogen sources yet display similar organization. How this is achieved is unclear and the relevant positional cues have not been identified. Here we show that intermediate progenitor domains are established through a distinct mechanism that operates in the preceding neural plate stage and leverages its multiple signaling inputs and morphogenesis. An integrated spatial atlas of transcription factor expression, signaling activity, and cell movement reveals that the neural plate comprises an array of cell states, defined by combinatorial signaling and morphogenesis-driven transitions between local signaling environments. Specifically, we find that p0 and p1 intermediate progenitors, located immediately outside the morphogen-patterned region, arise from specific precursor states that are established in the posterior neural plate by tailbud-derived Wnt signaling. Convergent-extension movements subsequently drive progenitor specification by displacing precursors out of Wnt/FGF signaling fields while shaping them into stripe-like domains. Thus, by controlling signaling exposure, tissue dynamics convert positional information encoded by signaling history into downstream fate specification. This mode of patterning may operate broadly across developmental contexts, with implications for tissue engineering and patterning-related disorders.

developmental biology↗

An adhesion code ensures robust pattern formation during tissue morphogenesis

An outstanding question in embryo development is how spatial patterns are formed robustly. In the zebrafish spinal cord, neural progenitors form stereotypic stripe-like patterns despite noisy morphogen signaling and large-scale cellular rearrangement required for tissue growth and morphogenesis. We set out to understand the mechanisms underlying this patterning robustness. Our adhesion assays revealed a preference for three neural progenitor types to stabilize contacts with cells of the same type. Genetic analysis uncovered a three-molecule adhesion code, composed of N-cadherin, Cadherin 11, and Protocadherin 19, with unique gene expression profiles for each cell type. Perturbation of the adhesion code results in loss of homotypic preference ex vivo and patterning errors in vivo. Both the cell fate and adhesion code are co-regulated by the common upstream morphogen signal Shh. We propose that robust patterning in tissues undergoing morphogenesis results from a previously unappreciated interplay between morphogen gradient-based patterning and adhesion-based self-organization.

developmental biology↗