Dr Georg Halder
Department of Biochemistry and Molecular Biology
The University of Texas&s_comma; M.D. Anderson Cancer Center&s_comma; Houston&s_comma; TX
Mysteries in Growth Control
The regulation of organ size is fundamental to animal development&s_comma; yet
remarkably little is known about the mechanisms that control organ size. How
do cells know when to stop dividing after an organ has reached its proper
size and how do injured organs regenerate missing or damaged parts? The
answers to these questions are currently unknown&s_comma; but it is thought that
neighboring cells signal to each other to regulate cell proliferation.
However&s_comma; the nature of these signals and how they regulate organ growth is
not known. Through a genome wide genetic screen in Drosophila&s_comma; we
discovered a new signal transduction pathway&s_comma; the Hippo pathway&s_comma; which is
essential for the development of properly-sized organs. Animals carrying
mutations in Hippo pathway components develop severely overgrown adult
structures because cells proliferate beyond normal organ size. We have
identified several components of the Hippo pathway and a signal transduction
pathway from the plasma membrane to the nucleus has begun to emerge. Most
interestingly&s_comma; we have recently identified a cell surface receptor that
regulates the activity of the Hippo pathway: the atypical Cadherin Fat. We
are currently addressing how the activity of Fat is regulated and what
ligands signal through Fat to regulate organ growth. We are also studying
how the Hippo pathway is involved in the regeneration of damaged tissues and
how it regulates cell cycle progression and organ growth.
1. Hamaratoglu F&s_comma; Kango-Singh M&s_comma; Nolo R&s_comma; Hyun E&s_comma; Tao C&s_comma; Jafar-Nejad H&s_comma; and
Halder G (2006). The tumour suppressor genes NF2/Merlin and Expanded act
through Hippo signalling to regulate cell proliferation and apoptosis.
Nature Cell Biology&s_comma; 8:27-36.
1. Nolo R&s_comma; Morrison C&s_comma; Tao C&s_comma; Zhang X&s_comma; Halder G (2006). The bantam microRNA
is a target of the Hippo tumor suppressor pathway. Current Biology 16&s_comma;
1. Willecke M&s_comma; Hamaratoglu F&s_comma; Kango-Singh M&s_comma; Udan R&s_comma; Chen CL&s_comma; Tao C&s_comma; Zhang
X&s_comma; and Halder G (2006). The Fat Cadherin acts through the Hippo tumor
suppressor pathway to regulate tissue size. Current Biology 16&s_comma; 2090-100.
1. Anbanandam A&s_comma; Albarado DC&s_comma; Nguyen CT&s_comma; Halder G&s_comma; Gao X&s_comma; Veeraraghavan S
(2006). Insights into transcription enhancer factor 1 (TEF-1) activity from
the solution structure of the TEA domain. Proc Natl Acad Sci USA 103&s_comma;
1. Childress JL&s_comma; Acar M&s_comma; Tao C&s_comma; Halder G (2006). Lethal giant discs&s_comma; a novel
C2 domain protein&s_comma; restricts Notch activation during endocytosis. Current
Biology 16&s_comma; 2228-33.
東京大学 分子細胞生物学研究所 形態形成研究分野
Phone:03-5841-7886 (Office)&s_comma; -7866&s_comma; -7896 (Lab)