Takako Makita

Assistant Professor

Pediatrics, Keck School of Medicine
Childrens Hospital Los Angeles

Research Topics

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

Research Overview

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 and in adult nerve injury repair, and for tissue/organ transplantations in humans.