PROJECT SUMMARY
An important question in developmental biology is how cell fate specification and cell movement are
coordinated during tissue morphogenesis to ensure all cell types reach their desired positions properly. One
example of this elegant coordination is the patterning of neural progenitors in the zebrafish spinal cord. In this
proposal, I will combine biophysical and genetic approaches to understand how cell fate specification and cell
adhesion are coordinated in the zebrafish neural tube. Studies from my early postdoctoral training have
identified E-cadherin (Cdh1), N-cadherin (Cdh2), and their transcriptional regulators as critical mediators for
patterning of neural progenitor domains. Building on these initial findings, this proposal aims to obtain a multi-
scale understanding of spinal cord pattern formation from the differential adhesion forces mediated by Cdh1
and Cdh2 in different neural progenitor cell types (Aim1), to the gene regulatory network controlling the spatial
patterns of Cdh1 and Cdh2 expressions (Aim2), to a computational framework to simulate cell sorting at the
tissue scale (Aim1). The experimental platform established in Aims 1 and 2 will be used to characterize novel
regulators of cell adhesion dynamics during spinal cord pattern formation and morphogenesis (Aim 3).
This proposal will combine my analytical skills developed as a graduate student to analyze spatiotemporal
dynamics of adhesion molecules at cellular and subcellular levels, the experimental knowledge acquired during
my early postdoctoral training to genetically engineer zebrafish and image live embryos with single cell
resolution, and the proposed training during the K99 mentored phase to probe cell mechanics and optically
perturb gene expression at high spatiotemporal precision. The training during the K99 mentored phase will
integrate the expertise of all four of my co-mentors and will complement my past training to form a complete
research program in my own independent lab to measure, perturb, and model spatiotemporal dynamics of
adhesion molecules in neural progenitor cells during spinal cord development.
My plan for transitioning to independence include professional trainings from all four of my co-mentors to
mentor students, manage labs, write grants, publish papers, present research results in conferences, and
establish scientific collaborations. By learning and interacting with all four co-mentors in different academic
institutes, I will combine their strength to formulate my own lab culture and mentoring style.
My long-term career goal is to direct a multidisciplinary research program studying the control of
spatiotemporal dynamics of cellular and subcellular events underlying robust embryo development. So far I
have achieved significant progress towards this goal in the form of research experience, successful
publications, and initiation of collaborations. I firmly believe, however, that a K99 mentored phase will help
maximize my chances for success by providing access to additional mentorship and training that would be
otherwise lacking from my current postdoctoral experience.