Makita Lab

RESEARCH TOPICS

Neurovascular interactions in growth and guidance of sympathetic axons from the superior sympathetic ganglia
Autonomic (sympathetic and parasympathetic) innervations of the heart and thorax
Sympathetic innervation of the kidney
Development of enteric nervous system
Growth and guidance of cutaneous sensory axons of the radial nerve of the forelimb
Axon guidance of the cranial nerves

RESEARCH OVERVIEW

Whole mount staining reveals the pattern of developing peripheral nervous system of the mouse embryo. A key process in developmental neurobiology is the manner by which axons projecting from newly born neurons choose routes to reach and ultimately innervate distant target organs. This process is called axon guidance and is characterized by the importance of instructional cues that direct axonal outgrowth. Only a limited number of guidance molecules are currently known, far less than sufficient to explain the complexity of the nervous system.

One of our major projects addresses the critical role of endothelin signaling in axon guidance. Endothelins are small bioactive peptides that play important roles in numerous developmental, physiological, and pathological events by interacting with specific cell surface receptors (endothelin receptors) that are members of the G-protein coupled receptor family. Although the biochemistry of endothelin signaling is well characterized in other contexts, prior to our work there was no indication that endothelins were involved in axon guidance, and therefore, little is known of how these biochemical properties are connected to the biological roles of endothelins in neural development.

My lab uses mouse genetics to dissect the biological roles of endothelin signaling in neural development, and molecular and biochemistry approaches to understand the underlying mechanisms in each process. Our work has therapeutic application to axon regeneration in several congenital neurological disorders, in nerve injury repair and for tissue/organ transplantation in humans.

ACHIEVEMENTS

A parasympathetic (the Xth cranial) ganglion grown in the presence of endothelins. Similar to sympathetic neurons, parasympathetic neurons require endothelins for growth in vivo and in vitro. Takako Makita, PhD, of Johns Hopkins School of Medicine, joined the Neuroscience Program at The Saban Research Institute. Her research focuses on neuro-vascular interactions during embryonic development. Makita’s work on the role of endothelins as axonal guidance cues for sympathetic axons was published in Nature.

Dr. Makita is analyzing cellular signaling events that direct development of the peripheral neural system. Her studies someday could have therapeutic application in congenital neurological disorders, nerve injury repair and tissue transplantation.

EDUCATION

University of Southern California, PhD, 2004

Tokyo Metropolitan, University, BS, 1995

PUBLICATIONS

Makita, T, Sucov, H.M, Gariepy, CE, Yanagisawa, M, and Ginty, DD (2007). Endothelins are vascular-derived axonal guidance cues for developing sympathetic neurons. Nature 452: 759-63, 2008.
Choudhary, B, Ito, Y, Makita, T, Sasaki, T, Chai, Y., and Sucov, HM (2006). Cardiovascular malformations with normal smooth muscle differentiation in neural crestspecific
type II TGFbeta receptor (Tgfbr2) mutant mice. Dev. Biol., 289:420-9.
Makita, T, Duncan, SA, and Sucov, HM (2005). Retinoic acid, hypoxia and GATA factors cooperatively control the onset of fetal liver erythropoietic differentiation. Dev. Biol.,
280:59-72.
Chen, TH, Chang, TC, Kang, JO, Choudhary, B, Makita, T, Tran, CM, Burch, JB, Eid, H, and Sucov, HM (2002). Epicardial induction of fetal cardiomyocyte proliferation via a retinoic acid-inducible trophic factor. Dev. Biol., 250:198-207.
Huang, J, Powell, WC, Khodavirdi, AC, Wu, J, Makita, T, Cardiff, RD, Cohen, MB, Sucov, HM, and Roy-Burman, P (2002). Prostatic intraepithelial neoplasia in mice with
conditional disruption of the retinoid X receptor alpha allele in the prostate epithelium. Cancer Res., 62:4812-9.
Makita, T, Hernandez-Hoyos, G, Chen, TH, Wu, H, Rothenberg, EV, and Sucov, HM (2001). A developmental transition in definitive erythropoiesis: erythropoietin expression is sequentially regulated by retinoic acid receptors and HNF4. Genes Dev., 15:889-901.

CONTACT US

Takako Makita, PhD Lab
The Saban Research Institute
4650 Sunset Boulevard
MS #135
Los Angeles, CA 90027
Fax: 323-361-1549
Email: Takako Makita, PhD