Takashi Mikawa, PhD

Professor
Cardiovascular Research Institute
+1 415 476-3230

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.

Research Summary: 
Developmental Regulation of Organogenesis
Publications: 

Mitotic antipairing of homologous and sex chromosomes via spatial restriction of two haploid sets.

Proceedings of the National Academy of Sciences of the United States of America

Hua LL, Mikawa T

Dynamic Cellular Integration Drives Functional Assembly of the Heart's Pacemaker Complex.

Cell reports

Bressan M, Henley T, Louie JD, Liu G, Christodoulou D, Bai X, Taylor J, Seidman CE, Seidman JG, Mikawa T

Chromosome Painting of Mouse Chromosomes.

Methods in molecular biology (Clifton, N.J.)

Hua LL, Mikawa T

Avians as a model system of vascular development.

Methods in molecular biology (Clifton, N.J.)

Bressan M, Mikawa T

Early divergence of central and peripheral neural retina precursors during vertebrate eye development.

Developmental dynamics : an official publication of the American Association of Anatomists

Venters SJ, Mikawa T, Hyer J

Reciprocal myocardial-endocardial interactions pattern the delay in atrioventricular junction conduction.

Development (Cambridge, England)

Bressan M, Yang PB, Louie JD, Navetta AM, Garriock RJ, Mikawa T

Induction of the Proepicardium.

Journal of developmental biology

Maya-Ramos L, Cleland J, Bressan M, Mikawa T

Isolation and culture of mouse proepicardium using serum-free conditions.

Methods (San Diego, Calif.)

Garriock RJ, Mikawa T, Yamaguchi TP

Early arterial differentiation and patterning in the avian embryo model.

Seminars in cell & developmental biology

Garriock RJ, Mikawa T

A dual role for ErbB2 signaling in cardiac trabeculation.

Development (Cambridge, England)

Liu J, Bressan M, Hassel D, Huisken J, Staudt D, Kikuchi K, Poss KD, Mikawa T, Stainier DY

An anteroposterior wave of vascular inhibitor downregulation signals aortae fusion along the embryonic midline axis.

Development (Cambridge, England)

Garriock RJ, Czeisler C, Ishii Y, Navetta AM, Mikawa T

Morphogenesis and cytodifferentiation of the avian retinal pigmented epithelium require downregulation of Group B1 Sox genes.

Development (Cambridge, England)

Ishii Y, Weinberg K, Oda-Ishii I, Coughlin L, Mikawa T

Notochord-derived BMP antagonists inhibit endothelial cell generation and network formation.

Developmental biology

Bressan M, Davis P, Timmer J, Herzlinger D, Mikawa T

Endothelial cell lineages of the heart.

Cell and tissue research

Ishii Y, Langberg J, Rosborough K, Mikawa T

Induction of proepicardial marker gene expression by the liver bud.

Development (Cambridge, England)

Ishii Y, Langberg JD, Hurtado R, Lee S, Mikawa T

Development of the cardiac conduction system.

Seminars in cell & developmental biology

Mikawa T, Hurtado R

FGF-mediated induction of ciliary body tissue in the chick eye.

Developmental biology

Dias da Silva MR, Tiffin N, Mima T, Mikawa T, Hyer J

Bone marrow Oct3/4+ cells differentiate into cardiac myocytes via age-dependent paracrine mechanisms.

Circulation research

Pallante BA, Duignan I, Okin D, Chin A, Bressan MC, Mikawa T, Edelberg JM

Enhanced sensitivity and stability in two-color in situ hybridization by means of a novel chromagenic substrate combination.

Developmental dynamics : an official publication of the American Association of Anatomists

Hurtado R, Mikawa T

TrkB/BDNF signaling regulates photoreceptor progenitor cell fate decisions.

Developmental biology

Turner BA, Sparrow J, Cai B, Monroe J, Mikawa T, Hempstead BL

VEGF family members regulate myocardial tubulogenesis and coronary artery formation in the embryo.

Circulation research

Tomanek RJ, Ishii Y, Holifield JS, Sjogren CL, Hansen HK, Mikawa T

Somatic transgenesis in the avian model system.

Birth defects research. Part C, Embryo today : reviews

Ishii Y, Mikawa T

Developmental transitions in electrical activation patterns in chick embryonic heart.

The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology

Sedmera D, Reckova M, Bigelow MR, Dealmeida A, Stanley CP, Mikawa T, Gourdie RG, Thompson RP

A role for Tbx5 in proepicardial cell migration during cardiogenesis.

Physiological genomics

Hatcher CJ, Diman NY, Kim MS, Pennisi D, Song Y, Goldstein MM, Mikawa T, Basson CT

Negative regulation of midline vascular development by the notochord.

Developmental cell

Reese DE, Hall CE, Mikawa T

Folding of the tectal cortex by local remodeling of neural differentiation.

Developmental dynamics : an official publication of the American Association of Anatomists

Mima T, Mikawa T

Induction and patterning of the primitive streak, an organizing center of gastrulation in the amniote.

Developmental dynamics : an official publication of the American Association of Anatomists

Mikawa T, Poh AM, Kelly KA, Ishii Y, Reese DE

Somatic transgenesis using retroviral vectors in the chicken embryo.

Developmental dynamics : an official publication of the American Association of Anatomists

Ishii Y, Reese DE, Mikawa T

Platelet-derived growth factor-AB promotes the generation of adult bone marrow-derived cardiac myocytes.

Circulation research

Xaymardan M, Tang L, Zagreda L, Pallante B, Zheng J, Chazen JL, Chin A, Duignan I, Nahirney P, Rafii S, Mikawa T, Edelberg JM

Hemodynamic-dependent patterning of endothelin converting enzyme 1 expression and differentiation of impulse-conducting Purkinje fibers in the embryonic heart.

Development (Cambridge, England)

Hall CE, Hurtado R, Hewett KW, Shulimovich M, Poma CP, Reckova M, Justus C, Pennisi DJ, Tobita K, Sedmera D, Gourdie RG, Mikawa T

Evidence for an extracellular matrix bridge guiding proepicardial cell migration to the myocardium of chick embryos.

Developmental dynamics : an official publication of the American Association of Anatomists

Nahirney PC, Mikawa T, Fischman DA

Optic cup morphogenesis requires pre-lens ectoderm but not lens differentiation.

Developmental biology

Hyer J, Kuhlman J, Afif E, Mikawa T

Fibroblast growth factor (FGF)-4 can induce proliferation of cardiac cushion mesenchymal cells during early valve leaflet formation.

Developmental biology

Sugi Y, Ito N, Szebenyi G, Myers K, Fallon JF, Mikawa T, Markwald RR

His-Purkinje lineages and development.

Novartis Foundation symposium

Gourdie RG, Harris BS, Bond J, Edmondson AM, Cheng G, Sedmera D, O'Brien TX, Mikawa T, Thompson RP

Induction and patterning of the Purkinje fibre network.

Novartis Foundation symposium

Mikawa T, Gourdie RG, Takebayashi-Suzuki K, Kanzawa N, Hyer J, Pennisi DJ, Poma CP, Shulimovich M, Diaz KG, Layliev J, Prasad A

Development of the coronary vessel system.

Circulation research

Reese DE, Mikawa T, Bader DM

Induction and patterning of the cardiac conduction system.

The International journal of developmental biology

Pennisi DJ, Rentschler S, Gourdie RG, Fishman GI, Mikawa T

Competency of embryonic cardiomyocytes to undergo Purkinje fiber differentiation is regulated by endothelin receptor expression.

Development (Cambridge, England)

Kanzawa N, Poma CP, Takebayashi-Suzuki K, Diaz KG, Layliev J, Mikawa T

Cell death along the embryo midline regulates left-right sidedness.

Developmental dynamics : an official publication of the American Association of Anatomists

Kelly KA, Wei Y, Mikawa T

TBX5 transcription factor regulates cell proliferation during cardiogenesis.

Developmental biology

Hatcher CJ, Kim MS, Mah CS, Goldstein MM, Wong B, Mikawa T, Basson CT

Fate diversity of primitive streak cells during heart field formation in ovo.

Developmental dynamics : an official publication of the American Association of Anatomists

Wei Y, Mikawa T

Trk C receptor signaling regulates cardiac myocyte proliferation during early heart development in vivo.

Developmental biology

Lin MI, Das I, Schwartz GM, Tsoulfas P, Mikawa T, Hempstead BL

Axonal growth of the spinal cord interneurons expressing a homophilic adhesion molecule SC1 ectopically.

Neuroscience research

Fujii T, Funahashi J, Matsuura R, Izaki T, Nakamura H, Mikawa T, Tanaka H

In vivo induction of cardiac Purkinje fiber differentiation by coexpression of preproendothelin-1 and endothelin converting enzyme-1.

Development (Cambridge, England)

Takebayashi-Suzuki K, Yanagisawa M, Gourdie RG, Kanzawa N, Mikawa T

Trk C signaling is required for retinal progenitor cell proliferation.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Das I, Sparrow JR, Lin MI, Shih E, Mikawa T, Hempstead BL

Stable transfectants of smooth muscle cell line lacking the expression of myosin light chain kinase and their characterization with respect to the actomyosin system.

The Journal of biological chemistry

Kishi H, Mikawa T, Seto M, Sasaki Y, Kanayasu-Toyoda T, Yamaguchi T, Imamura M, Ito M, Karaki H, Bao J, Nakamura A, Ishikawa R, Kohama K

Retroviral cell lineage analysis in the developing chick heart.

Methods in molecular biology (Clifton, N.J.)

Gourdie RG, Cheng G, Thompson RP, Mikawa T

Induction of Purkinje fiber differentiation by coronary arterialization.

Proceedings of the National Academy of Sciences of the United States of America

Hyer J, Johansen M, Prasad A, Wessels A, Kirby ML, Gourdie RG, Mikawa T

Development of the cardiac conduction system involves recruitment within a multipotent cardiomyogenic lineage.

Development (Cambridge, England)

Cheng G, Litchenberg WH, Cole GJ, Mikawa T, Thompson RP, Gourdie RG

Adenovirus-mediated gene transfer of a truncated form of fibroblast growth factor receptor inhibits growth of glioma cells both in vitro and in vivo.

Journal of neuro-oncology

Saiki M, Mima T, Takahashi JC, Tani S, Yukawa H, Ueno H, Mikawa T, Itoh N, Kikuchi H, Hashimoto N, Miyatake S

Conducting the embryonic heart: orchestrating development of specialized cardiac tissues.

Trends in cardiovascular medicine

Gourdie RG, Kubalak S, Mikawa T

Neural crest cells in outflow tract septation of the embryonic chicken heart: differentiation and apoptosis.

Developmental dynamics : an official publication of the American Association of Anatomists

Poelmann RE, Mikawa T, Gittenberger-de Groot AC

Endothelin-induced conversion of embryonic heart muscle cells into impulse-conducting Purkinje fibers.

Proceedings of the National Academy of Sciences of the United States of America

Gourdie RG, Wei Y, Kim D, Klatt SC, Mikawa T

FGF1 patterns the optic vesicle by directing the placement of the neural retina domain.

Development (Cambridge, England)

Hyer J, Mima T, Mikawa T

Trabecular myocytes of the embryonic heart require N-cadherin for migratory unit identity.

Developmental biology

Ong LL, Kim N, Mima T, Cohen-Gould L, Mikawa T

Skeletal muscle-specific myosin binding protein-H is expressed in Purkinje fibers of the cardiac conduction system.

Circulation research

Alyonycheva T, Cohen-Gould L, Siewert C, Fischman DA, Mikawa T

Retroviral vectors to study cardiovascular development.

Trends in cardiovascular medicine

Mikawa T, Hyer J, Itoh N, Wei Y

The polyclonal origin of myocyte lineages.

Annual review of physiology

Mikawa T, Fischman DA

Terminal diversification of the myocyte lineage generates Purkinje fibers of the cardiac conduction system.

Development (Cambridge, England)

Gourdie RG, Mima T, Thompson RP, Mikawa T

An additional limb can be induced from the flank of the chick embryo by FGF4.

Biochemical and biophysical research communications

Ohuchi H, Nakagawa T, Yamauchi M, Ohata T, Yoshioka H, Kuwana T, Mima T, Mikawa T, Nohno T, Noji S

Fibroblast growth factor receptor is required for in vivo cardiac myocyte proliferation at early embryonic stages of heart development.

Proceedings of the National Academy of Sciences of the United States of America

Mima T, Ueno H, Fischman DA, Williams LT, Mikawa T

Mapping the origin of the avian enteric nervous system with a retroviral marker.

Developmental dynamics : an official publication of the American Association of Anatomists

Epstein ML, Mikawa T, Brown AM, McFarlin DR

The major myosin-binding domain of skeletal muscle MyBP-C (C protein) resides in the COOH-terminal, immunoglobulin C2 motif.

The Journal of cell biology

Okagaki T, Weber FE, Fischman DA, Vaughan KT, Mikawa T, Reinach FC

Retroviral analysis of cardiac morphogenesis: discontinuous formation of coronary vessels.

Proceedings of the National Academy of Sciences of the United States of America

Mikawa T, Fischman DA

Clonal analysis of cardiac morphogenesis in the chicken embryo using a replication-defective retrovirus. III: Polyclonal origin of adjacent ventricular myocytes.

Developmental dynamics : an official publication of the American Association of Anatomists

Mikawa T, Cohen-Gould L, Fischman DA

Metanephric mesenchyme contains multipotent stem cells whose fate is restricted after induction.

Development (Cambridge, England)

Herzlinger D, Koseki C, Mikawa T, al-Awqati Q

Clonal analysis of cardiac morphogenesis in the chicken embryo using a replication-defective retrovirus: I. Formation of the ventricular myocardium.

Developmental dynamics : an official publication of the American Association of Anatomists

Mikawa T, Borisov A, Brown AM, Fischman DA

In vivo analysis of a new lacZ retrovirus vector suitable for cell lineage marking in avian and other species.

Experimental cell research

Mikawa T, Fischman DA, Dougherty JP, Brown AM