Chia-Teng Chang

Program: Developmental Regenerative and Stem Cell Biology

Current advisor: Tony Tsai, MD, PhD

Undergraduate university: National Taiwan University, 2017

Enrollment year: 2021

Research summary
The interplay between morphogen signaling and cell migration

Morphogen signaling directs cellular movements essential for tissue and organ formation. As cells
migrate in a developing organism, their changes in positions influence their response to these cues. This
research will investigate how morphogen signaling dynamically regulates cell movement and patterning,
focusing on BMP during gastrulation and Shh during spinal cord development in zebrafish.
Aim 1: How does BMP signaling regulate the gastrulation movements of three germ layers?
During gastrulation, cells undergo specific movements to shape the body plan—They either migrate
dorsally to form the body axis through convergence and extension (C&E) or move vegetally to form the
tail bud. The ventral to dorsal BMP signaling gradient directs these movements by inhibiting
mesoderm’s C&E and promoting vegetal migration cell-autonomously. Preliminary results further
suggest BMP signaling regulates ectoderm migration cell-autonomously and endoderm non-cell
autonomously. Notably, neuroectoderm cells receiving high BMP signaling sorted during neural plate
C&E, even though BMP signaling activity is absent during this phase, suggesting gastrulation patterning
influences cell movements during neurulation.
In 1A, I will investigate how BMP signaling regulates endodermal migration non-cell autonomously. I
hypothesize endodermal cells adhere to mesodermal cells via cadherins or ECM, which will be tested by
disrupting their adhesion. In 1B, I will identify genes regulated by BMP signaling in mesoderm using
optogenetic activation during C&E followed by single-cell RNA-seq. The identified genes will be
functionally tested for their role in mesoderm’s C&E. In 1C, I aim to identify BMP-regulated adhesion
molecules in neural ectoderm and assess their role in cell sorting during neurulation.
Aim 2: How do migrating cells interpret positional cues during spinal cord development?
The Shh gradient in the developing spinal cord encodes positional information along the dorsoventral
axis. However, significant morphological changes in the spinal cord complicate the interpretation of
these cues. My preliminary findings, based on in toto imaging and single-cell tracing, reveal that
positional information received by the cells in vivo does not increase monotonically over time, but
instead peaks halfway during the patterning process and then decreases. Referring to the history of cell
positions and signaling responses, the decrease in positional information is attributed to cell
rearrangement and heterogeneous changes in signaling responsiveness.
In 2A: I will assess how neural plate C&E affects the Shh gradient by inhibiting C&E to rescue
positional information. In 2B: I will determine if cell sorting helps establish or stabilize the Shh
signaling gradient by disrupting ventral spinal cord-expressed cadherins. In 2C: I will explore the
heterogeneity of Shh response post-neural plate C&E. I hypothesize Notch signaling mediates this
response, which will be tested by uniformly activating Notch in the neuroectoderm.
This study will shed light on the complex relationship between cell signaling and migration in
developmental biology. Aim 1 will clarify how BMP signaling can simultaneously guide the migration
of three germ layers, each with distinct signaling responses and migratory behaviors. Aim 2 will explore
how cells navigate the challenges of dynamic positional cues and varying signaling responsiveness
during spinal cord development. Overall, this research will provide a comprehensive framework for
understanding the mutual influence of signaling and migration, filling a critical gap in the field.

Graduate publications