Multi-cellular organ systems develop through non-steady state reactions that orchestrate the differentiation and integration of many cell types. Using the cardiovascular and central nervous systems as model organs, our group investigates specific reactions that define cell fate decision, cell size and shape, body axis formation, and faithful delivery of parental genomes to all daughter cells during organ formation. These include mechanisms responsible for: a) establishment of the midline identity along which the tubular organ primordium forms; b) subdivision of neural and non-neural zones within the retina, and segregation of pacemaker from ordinary heart muscle zones within cardiogenic mesoderm; c) diversification within clone units of the brain and heart into glial or neuronal cell fates (brain) or myocytes vs. impulse conducting cell linages (heart); d) formation, recruitment, and in situ patterning of an extra-cardiac progenitor population which establishes the coronary vascular network of the heart; and e) positioning of paternal and maternal chromosome during cell division.
1 - Formation of the avian primitive streak from spatially restricted blastoderm: evidence for polarized cell division in the elongating streak. Wei Y, Mikawa T. Development. 2000 volume 127, pages 87-96.
2 - Hemodynamic-dependent patterning of endothelin converting enzyme 1 expression and differentiation of impulse-conducting Purkinje fibers in the embryonic heart. Hall CE, Hurtado R, Hewett KW, Shulimovich M, Poma CP, Reckova M, Justus C, Pennisi DJ, Tobita K, Sedmera D, Gourdie RG, Mikawa T. Development. 2004. volume 131, pages 581-592.
3 - Negative regulation of midline vascular development by the notochord. Reese DE, Hall CE, Mikawa T. Developmental Cell. 2004 volume 6, pages 699-708.
4 - BMP signals promote proepicardial protrusion necessary for recruitment of coronary vessel and epicardial progenitors to the heart. Ishii Y, Garriock RJ, Navetta AM, Coughlin LE, Mikawa T. Developmental Cell, 2010 - Volume 19,2010, Pages 307–316.
5 - Early mesodermal cues assign avian cardiac pacemaker fate potential in a tertiary heart field. Bressan M, Liu G, Mikawa T. Science, 2013 Vol. 340 no. 6133 pp. 744-748.