• campus:  a to z index
• map
• directory
• calendar

Search:

Yukio Saijoh

Assistant Professor of Neurobiology and Anatomy

B.S. Tohoku University, Japan

Ph.D. Tohoku University, Japan

Research

References

y.saijoh@utah.edu

 

Research

My fundamental interest is in vertebrate pattern formation: how vertebrates make up their complicated and organized body plan. Embryogenesis requires correct cell differentiation and positioning of tissues and organs in three dimensions. These two events are closely related to each other and are regulated with respect to each of the three body axes: anterior-posterior, dorso-ventral, and left-right (L-R). A goal of my research is to understand the genetic cascade establishing left-right (L-R) asymmetries observed in the internal organs of vertebrates such as the heart and stomach. Defects in L-R axis result in disorganized morphology and malposition of organs disrupting their normal function. In humans, defects in L-R asymmetric patterning commonly cause birth defects of the heart, lungs, gut and other asymmetric organs.
The genetic cascade establishing initial L-R asymmetry has been identified over the last 10 years, but how L-R information regulates asymmetric morphogenesis in internal organs is poorly understood. My current emphasis is on studying how L-R signals regulate heart looping morphogenesis. Cardiac myocytes derived from the left and right cardiac fields fuse to form a symmetric single heart tube and then the tube loops rightward (Fig.A-C). To understand the morphogenesis of heart looping, I take several approaches using different model systems.

First, to understand dynamic morphogenesis, cell behavior during heart tube fusion and looping is investigated by cell tracing and cell proliferation experiments in the chick system, which is an ideal model to observe development in vivo and in culture. The ease with which chick embryos can be observed during cardiac development allows for direct observation of dye labeled cells under time-lapse video microscopy. To investigate the differences between the left and right sides of the heart more clearly, separated hearts in chick embryos are examined in culture (de Haan 1959). When cuts are made in the anterior boundary of the heart fields, left and right heart tubes fail to fuse and instead form independent left and right hearts with different morphology. The separated heart system is an excellent tool with which to investigate the differences between left and right heart. Analysis of gene expression and cell behavior in this system reveals how left and right heart tubes develop differently in heart looping morphogenesis.

Second, what we learn from chick experiments is transferred to studies in mice. Valuable genetic tools exist in mice, including mutant mice with laterality defects: randomization, situs inversus, and left and right isomerisms. To gain insight into how L-R signals regulate asymmetric morphogenesis, cell behavior in normal and mutant mouse embryos is examined in a whole embryo culture system. Cell movement is traced by fluorescent dyes combined with GFP proteins driven by a L-R asymmetric enhancer  (Fig. D).

Third, I also investigate molecular mechanisms underlying asymmetric cardiac morphogenesis. Nodal, a member of the TGF-beta superfamily is the determinant of L-R asymmetry in the left side. The P19CL6, an embryonic carcinoma stem cell line, shows efficient differentiation into beating cardiac myocytes after induction with DMSO. Using this system, the influence of Nodal signals on cardiac myocyte during differentiation is examined.

Finally, downstream genes of the Nodal signal in asymmetric heart morphogenesis are screened by use of chick, mouse and cell culture system.

 

(A-C) Heart looping morphogenesis in the chick embryo. (A) Left and right cardiac myocytes starts to fuse at the anterior region at stage 8. (B) Fused linear heart tube just before looping at stage 10. (C) The heart tube is looping toward the right side at stage 11. (D) Left sided LacZ reporter expression driven by the asymmetric enhancer of Lefty2. Expression includes a region of the fusing heart in 8 day mouse embryos.

References