Investigating morphogen and patterning dynamics with optogenetic control of morphogen production.

Morphogen gradients provide the patterning cues that instruct cell fate decisions during development. Here, we establish an optogenetic system for the precise spatiotemporal control in vitro of Sonic hedgehog (Shh) morphogen production. Using a tunable light-inducible gene expression system, we generate long-range Shh gradients that pattern mouse neural progenitors into spatially distinct domains, mimicking neural tube development. We investigate how biochemical features of Shh and Shh-interacting proteins affect patterning length scales. By measuring clearance rates, we determine that Shh has an extracellular half-life below 1.5 h, substantially shorter than downstream gene expression dynamics, indicating gradients are continually renewed during patterning. We provide evidence that progenitor identity acquisition and maintenance depend on both Shh concentration and exposure duration. Together, this approach provides a quantitative framework for investigating morphogen patterning, enabling reproducible control of morphogen dynamics to dissect the interplay between biochemical cues, gradient formation biophysics, and transcriptional programs underlying developmental patterning.

• Publication year

  2025

• Venue

  Developmental Cell

• Publication date

  2025-08-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.devcel.2025.07.019PMID 40848721
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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