Dr. Nathalia Glickman Holtzman
Ph.D., University of Oregon
Office: NSB E-102, Tel: 718 997 3678
Laboratory: NSB E-101, Tel: 718 997 3517
E-mail: nathalia.holtzman @ qc.cuny.edu
The process by which an organ forms is a fundamental question of developmental biology. Organogenesis requires the specification of diverse cell fates and a variety of coordinated cellular movements, cell shape changes, and cellular interactions. We have some insight into the patterning required for organ formation, but very little is known about how this patterning orchestrates the cell behaviors that underlie organ formation. Utilizing zebrafish as a model system, we integrate cell biology, embryology, genetics, time-lapse video microscopy and computer-based cell movement analysis to address two main questions:
What signals/patterning events direct cell movement during tissue morphogenesis?
How do the cells translate this information into directed movement?
Above is the heart of a normal zebrafish embryo antibody stained such that the entire heart (red) and just the atrium (green) are visualized. Normal cardiac morphology at 36 hours post fertilization is seen. In contrast, the embryo on the right demonstrates a condition called cardia bifida, where the two embryonic heart fields fail to meet at the midline, resulting in the production of two heart tubes. Note that atrium and ventricle is specified correctly in this mutant but cardiac morphology is disrupted.
During heart formation, cardiac precursors start out as bilateral sheets of cells that move toward the midline, where they converge, surround the central endocardium, and rearrange to create the heart tube. Though the tissue level shape changes that occur during heart tube formation are beginning to be understood, little is known about the cell behaviors or the molecular regulation of this process. Tracking the movement of individual GFP-expressing cardiomyocytes in wild-type zebrafish embryos and in zebrafish mutants with heart tube defects suggests that highly regulated, coordinated cell movements are required to form the heart.
We are currently examining the role of the endoderm, endocardium and yolk in directing the movement of the myocardium.
Nathalia Glickman-Holtzman’s lab was awarded a 3-year NIH R15 grant. Title: “Defining endocardail requirements for myocardial morphogenesis” in the Spring of 2009
C. Singleman and N.G. Holtzman. (2011) ” Heart Dissection in Larval, Juvenile and Adult Zebrafish, Danio rerio,” J Vis Exp. 2011 Sep 30;(55): e3165.
Nick Osborne1, Koroboshka Brand-Arzamendi, Elke A. Ober, Suk-Won Jin, Heather Verkade, Nathalia G. Holtzman, Deborah Yelon and Didier Y.R. Stainier. (2008). The Spinster Homolog, Two of Hearts, Is Required for Sphingosine 1-Phosphate Signaling in Zebrafish. Current Biology, 18: 1882-1888.
Baker, K., N.G. Holtzman, and R.D. Burdine. (2008). “Nodal Dependent and Independent Axis Conversions During Asymmetric Morphogenesis of the Zebrafish Heart.” PNAS, 105(37): 13924-9.
De Campos-Baptista, M.I., N.G. Holtzman, D. Yelon, and A.F. Schier. (2008). “Nodal signaling promotes the speed and directional movement of cardiomyocytes in zebrafish.” Dev Dyn. 237 (12) 3624 – 3633.
Holtzman, N.G., J.J. Schoenebeck, H.J. Tsai, and D. Yelon. (2007). Endocardium is necessary for cardiomyocyte movement during heart tube assembly. Development. 134(12):2379-86.
Glickman, N.S. and D. Yelon. (2004). Coordinating morphogenesis: epithelial integrity during heart tube assembly. Dev Cell. 6(3):311-2.
Glickman, N.S., C.B. Kimmel, M. Jones, C. Walker, and R.J. Adams. (2003). Shaping the zebrafish notochord. Development. 130(5):873-87.
Glickman, N.S. and D. Yelon. (2002). Cardiac development in zebrafish: coordination of form and function. Semin Cell Dev Biol. 13(6):507-13.