Holger Knaut, PhD
Assistant Professor of Cell Biology
Ph.D., 2001 Universität Tübingen/
Max-Planck Institute for Developmental Biology
Signal Transduction, Stem Cell Biology, Developmental neurobiology, Cell Migration, Morphogenesis
Chemokine Signaling, Head Myoblasts, Migration, Trigeminal Sensory Neurons
Skirball Institute of Biomolecular Medicine
New York University School of Medicine
540 First Ave. 4th floor
New York, NY 10016
Office Tel: (212) 263-7227
Fax: (212) 263-0614
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 two 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 muscle precursor migration as a second model, we study how very related cells migrate out and navigate to different targets in the embryo. Muscle precursor cells are confronted with such a challenge. They originate from the paraxial mesoderm and need to migrate to different positions in the head and appendages. Having reached their targets, they join with tendon precursors and attach to specific sites on the skeleton. Identifying the molecules and understanding the mechanisms that allow migrating muscle precursors to find and interact with their distinct targets will contribute to our understanding how complex structures are assembled.
Using genetic and embryological approaches combined with imaging we will dissect these two processes. Comparing the insights we gain will contribute to our understanding of how the embryo achieves two very different tasks: recruiting cells of different origin to form a functional unit and separating highly related cells to populate distinct positions to form a functional network. Ultimately, this knowledge can be applied to conditions in which organ formation goes awry.
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. 155(3):674-87. PMID: 24119842
Lewellis, S.W. Nagelberg, D., Subedi, A. Staton, A. LeBlanc, M. Giraldez, A. Knaut, H. (2013) Precise SDF1-mediated cell guidance is achieved through ligand clearance and miRNA-mediated decay. Journal of Cell Biology. 200(3):337-55. PMID: 23382464
Staton, A., Knaut, H. and Giraldez, A. J. (2011) miRNA regulation of Sdf1 chemokine signaling provides genetic robustness to germ cell migration. Nature Genetics. 43(3):204-11. PMID: 21258340
Knaut, H.*and Schier, A.F*. (2008) Clearing the path for germ cells. Cell. Feb 8; 132(3):337-9. PMID: 18267065