Yuh Nung Jan, PhD

Howard Hughes Investigator
Professor
Department of Physiology
+1 415 476-8747

We have been working on various aspects of developmental neurobiology, from neurogenesis, asymmetric cell division and more recently to neuronal morphogenesis and repairmen by using Drosophila. Initially, we focused on how neuronal cell fates are specified. In 1993, we discovered Atonal, which turns out to be the founding member of an important family of proneural genes including Neurogenin, Math 1 and Math 5. We also discovered the role of the homeodomain protein Cut in specifying subtypes of neurons. These studies provided insights to neuronal cell fate specification.

We next addressed the question of how do two daughters of a neural progenitor acquire different cell fates. We approached this problem by studying Drosophila sensory bristle, which is derived from a single precursor that goes through 4 divisions giving rise to 5 cells. Each division is asymmetric. We identified numb mutant, in which all the divisions become symmetrical. In 1994, we discovered that Numb is asymmetrically localized to one pole of the precursor cell and segregated into one of the daughter cells to make them different. This process is repeated in all the divisions of the sensory bristle linage as well as in the neuroblast divisions. Numb is the first cell fate determinant identified for asymmetric cell division in the nervous system. Subsequent studies by us and the others, concerning how Numb and other cell fate determinants are localized to one of the two daughter cells to specify their fates, have provided insights about the mechanisms of asymmetric cell division, a basic mechanism for generating cell diversity.

In the past 16 years, dendrite morphogenesis has become the main focus of our lab.   Dendrites are part of neuron used to receive signal. They are among the most beautiful structures in biology. Each type of neuron has distinct dendritic morphology. So dendrite morphology is a distinguishing hallmark of a neuron. Not much was known about the underlying mechanisms when we started studying this problem in 1999. We found that the dendritic arborization (da) neurons of the Drosophila larval PNS are very well suited for studying dendrite morphogenesis. Those neurons could be divided into 4 different classes based on their dendritic morphology. By using them, my colleagues and I have gained some insights about dendrite development. For example: how neurons with distinctive dendrite morphologies depend on their level of Cut expression for diverse dendrite branching complexities, how certain types of neurons exhibit homotypic repulsion of their dendrites to allow tiling of the dendritic field for maximal coverage without ambiguity, by revealing the essential role of the NDR family kinase Tricornered, how tiling and dendrite maintenance can be differentially regulated by the upstream NDR family kinase and tumor suppressor Hippo, and how a differential reliance on the secretory pathway contributes to the differentiation of axons and dendrites.  More recently, by taking advantage of the wealth of information gained from our study of normal dendrite morphogenesis, we have begun to study the molecular mechanisms controlling the regeneration of axons and dendrites after injury.

Primary Thematic Area: 
Neurobiology
Secondary Thematic Area: 
Developmental & Stem Cell Biology
Research Summary: 
We are interested in the mechanisms underlying normal development of the nervous system and use that information to gain insights about the cellular and molecular causes of neurological disorders, and the regulation of axon and dendrite regeneration.
Featured Publications: 

Ankyrin Repeats Convey Force to Gate the NOMPC Mechanotransduction Channel.

Cell

Zhang W, Cheng LE, Kittelmann M, Li J, Petkovic M, Cheng T, Jin P, Guo Z, Göpfert MC, Jan LY, Jan YN

Regulation of axon regeneration by the RNA repair and splicing pathway.

Nature neuroscience

Song Y, Sretavan D, Salegio EA, Berg J, Huang X, Cheng T, Xiong X, Meltzer S, Han C, Nguyen TT, Bresnahan JC, Beattie MS, Jan LY, Jan YN

Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons.

Neuron

Meltzer S, Yadav S, Lee J, Soba P, Younger SH, Jin P, Zhang W, Parrish J, Jan LY, Jan YN

Phosphorylation of ß-Tubulin by the Down Syndrome Kinase, Minibrain/DYRK1a, Regulates Microtubule Dynamics and Dendrite Morphogenesis.

Neuron

Ori-McKenney KM, McKenney RJ, Huang HH, Li T, Meltzer S, Jan LY, Vale RD, Wiita AP, Jan YN

In vivo dendrite regeneration after injury is different from dendrite development.

Genes & development

Thompson-Peer KL, DeVault L, Li T, Jan LY, Jan YN