Assistant Professor; Skirball Institute of Biomolecular Medicine, Developmental Genetics. Department of Cell Biology
Ph.D., 2001 Universitat Tubingen / Max-Planck Institute for Developmental Biology
Cranial muscles, sensory neurons, chemokine signaling, cell migration, Cranial blood vessels
Skirball Institute of Biomolecular Medicine
540 First Avenue 4th floor, Lab 15
New York, N.Y. 10016
Office Tel: (212) 263-7227
Lab Tel: (212) 263-3506
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Tel: (646) 501-0679
In vivo analysis of dynamic processes that shape complex structures in zebrafish
Embryonic development involves extensive cell and tissue movements. Cells are often born far from their final position and face the challenge of navigating through the embryo to reach their destination and assemble into organs. To accomplish this task, they have to correctly interpret guidance cues and interact with various tissues along their migratory route.
Our goal is to understand how cells solve this task in three different scenarios:
1. Using trigeminal sensory ganglion assembly as a model, we study how disperse cells migrate to join and form a functional unit. Trigeminal sensory neurons face such a challenge. They are born from two different cell populations that need to join and assemble into a correctly positioned ganglion. Understanding this process on a cellular and molecular level will contribute to our knowledge of how migrating cells of different types interact with each other and the tissues they encounter en route to assemble into an organ.
2. Using the lateral line primordium as a model, we study how a group of about 100 cells migrates as a coherent unit. The primordium faces this challenge. It migrates as an epithelial-like sheet from behind the ear to the tip of the tail of the embryo. For this, the cells in the primordium need to sense directional cues and coordinate their movement with each other. Unraveling how cells cooperate to move as groups will contribute to our basic understanding of how organs form during development, tumors metastasize during disease and wounds close upon injury.
3. Using head mesoderm migration as a second model, we study how very related cells migrate out and navigate to different targets in the embryo. Head mesoderm cells are confronted with such a challenge. They are born next to the brain and need to migrate to different positions in the head, where they form muscles, blood vessels and part of the heart. Identifying the molecules and understanding the mechanisms that divides the head mesoderm into different cell populations that need to migrate to different targets will contribute to our understanding of how the head and heart are formed.
We are dissecting these three processes by combining genetic and embryological approaches with quantitative imaging and modeling. Comparing the insights we gain will contribute to our biophysical, molecular and cellular understanding of how cells migrate as individuals and groups. Ultimately, this knowledge can be applied to conditions in which cell migration goes awry.
- Nagelberg D, Wang J, Su R, Torres-Vázquez J, Targoff KL, Poss KD, Knaut H. Origin, Specification, and Plasticity of the Great Vessels of the Heart. Curr Biol. 2015 Aug 17;25(16):2099-110. doi: 10.1016/j.cub.2015.06.076. Epub 2015 Aug 6. PMID: 26255850
- Wang J, Knaut H. Chemokine signaling in development and disease. Development. 2014 Nov;141(22):4199-205. doi: 10.1242/dev.101071. PMID: 25371357
- Venkiteswaran G, Lewellis SW, Wang J, Reynolds E, Nicholson C, Knaut H. Generation and Dynamics of an Endogenous, Self-Generated Signaling Gradient across a Migrating Tissue. Cell, 10 October 2013. PMID: 24119842
- Lewellis, S.W. Nagelberg, D., Subedi, A. Staton, A. LeBlanc, M. Giraldez, A. Knaut, H. (2013) Precision in SDF1 cell guidance through ligand clearance and miRNA regulation. Journal of Cell Biology. 200(3):337-55. PMID: 23382464