Developmental Biology Program

Address

The Children’s Hospital of Philadelphia
Abramson Research Center, Rm 512
3615 Civic Center Boulevard
Philadelphia, Pa 19104
(215) 590-5671

Office tel.: (215) 590-4307
Fax: (215) 590-3709
E-mail:goldenj@mail.med.upenn.edu


Link(s)

Lab

Developmental Biology at CHOP

Research Interests

• Patterning and cell migration in the developing nervous system

Search PubMed for articles

Description of Research

My laboratory is interested in understanding multiple aspects of early nervous system development. The first area of focus is in patterning the rostral neural tube. The neural tube receives specific positional information defining the rostral-caudal, dorsal-ventral and left-right axes. The specification of these axes results from the coordinated action of many genes with precise temporal and spatial expression patterns during development. To investigate dorsal-ventral patterning in the forebrain we have used a combination of studies in the chick and mouse embryos. The chick embryos allow us to easily perform misexpression studies using electroporation and by the introduction of viral vectors to test the role of specific genes. Furthermore, the chick lends itself to experimental manipulation and many years of well-defined anatomical studies. More recently we have turned to the mouse to take advantage of genetics, allowing us to use transgenic and conditional mutagenesis to affect specific genes at specific times in development. To date we have focused primarily on the BMP signaling pathway and have recently identified new modulators of this pathway. These studies have allowed us to gain a greater insight into the molecular regulation of patterning the forebrain, and studies from our lab and other labs have confirmed that disruption of patterning results in anomalies in brain development. Studying these disruptions will allow us to better understand the pathogenesis of human diseases including brain malformations, mental retardation, epilepsy and autism.

The second focus of the laboratory is on the molecular and cellular mechanisms of cell migration. We use a combination of in vivo and in vitro methods to study cell migration. Over the past few years we have established the developmental timing of non-radial cell migration in the chick embryo and have identified at least one molecule, DM-GRASP, required for this migration. We also found axons were the most likely guide for non-radial cell migration in the chick. Again turning to the mouse model to take advantage of the power of mouse genetics, we have conclusively shown that at least some populations of interneurons use axons for their migration. We have gone on to look at the intracellular signaling required for cell migration and have shown Lis1 is necessary for normal cell migration. Current studies are focused on understanding the role of other candidate genes in the Lis1 pathway as well as several transcription factors such as Arx. These studies have lead to new insights into the pathogenesis of human disorders such as lissencephaly, mental retardation, and several epilepsy syndromes.

Recent Publications

Lindsten T.*, Golden J.A.*, Zong W-X., Minarcik J., Harris M.H., Thompson C.B. The proapoptotic activities of Bax and Bak limit the size of the neural stem cell pool. J. Neuroscience, 23:11112-9, 2003. (*these authors contributed equally to this manuscript).

McManus M.F., Nasrallah I.M., Gopal P., Baek W.S., Golden J.A. Inhibitory interneurons migrate on specific neurons. J Neuropathol Exp Neurol. 63:932-41, 2004.

McManus M.F.*, Nasrallah I.M.*, Pancoast M., Wynshaw-Boris A., Golden J.A. Lis1 Is Necessary for Normal Non-Radial Migration of Inhibitory Interneurons. Am J Pathol. 165:775-84, 2004. (*these authors contributed equally to this manuscript).

Nasrallah I.M., Minarcik J.C., Golden J.A. A polyalanine tract expansion in Arx forms intranuclear inclusions and results in increased cell death. J Cell Biol. 167:411-6, 2004.

Lim Y., Cho G, Minarcik J.C., Golden J.A. Altered BMP Signaling Disrupts Chick Diencephalic Development. Mech Development. 122:603-20, 2005.

Lab

Various cell and molecular biology projects related to cell migration and patterning in the developing nervous system.

Jeremy Minacik, Technician
William Shapiro, Technician
Pallavi Gopal, Graduate Student
Youngshin Lim, Ph.D., Postdoc
Ginam Cho, Ph.D., Postdoc
Carl Fulp, Graduate Student