Abstract

Patterning and morphogenesis occur concurrently during embryonic development. In many contexts, both processes are regulated by morphogen signaling: morphogens specify spatially organized cell identities while also influencing the cell behaviors that shape tissues. This creates a reciprocal problem. Morphogen signaling can affect how cells move, while cell movement can change how cells experience and interpret morphogen signals. This dissertation investigates this reciprocal problem during zebrafish gastrulation and neurulation. First, it examines how the ventral-to-dorsal bone morphogenetic protein (BMP) activity gradient regulates germ-layer morphogenesis during gastrulation. BMP signaling is known to pattern dorsal–ventral cell fate and regulate mesodermal convergence and extension (C&E), but whether BMP controls movement through earlier fate specification or through more direct regulation of migration remained unclear. In addition, how BMP influences endodermal morphogenesis was poorly understood. This work shows that BMP activity regulates both mesodermal and endodermal distribution and movement during C&E. Temporally controlled BMP activation further demonstrates that BMP can rapidly redirect mesodermal and endodermal cell migration during gastrulation. BMP acts more directly on mesoderm in a cell-autonomous fashion, whereas endodermal movement is largely coordinated through non-cell-autonomous interactions with mesoderm. Second, this dissertation examines how morphogenesis influences morphogen interpretation during neurulation. Sonic hedgehog (Shh) signaling patterns ventral spinal cord progenitors while the neural plate converges and transforms into a neural tube. Because cells change position relative to the Shh source during this process, whether a cell’s signaling history remains predictive about its final position and fate is unclear. Using lineage-resolved measurements of Shh response, cell position, and fate, this work shows that Shh-encoded positional information peaks early during neurulation and then declines despite increasing Shh response. Cell rearrangements impose a limit on how precisely Shh signaling can predict final position and fate, while later heterogeneity in Shh responsiveness further limits information accumulation. Fate specification occurs during this early window of maximal positional information. Together, these studies demonstrate how morphogen signaling and morphogenesis can regulate each other during development. BMP signaling instructs germ-layer movements during gastrulation, while neural plate morphogenesis determines when Shh signaling is most informative during spinal cord patterning. Thus, embryonic development depends on both morphogen gradients and the dynamic tissue context in which cells interpret them.

Committee Chair

Tony Tsai

Committee Members

Lilianna Solnica-Krezel, Carl-Philipp Heisenberg; Geoffrey Goodhill; Gregory Longmore

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Developmental, Regenerative, & Stem Cell Biology)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

8-11-2026

Language

English (en)

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