The mammalian brain is an extremely complex structure both anatomically and functionally, that simultaneously integrates multiple inputs to produce an appropriate response. Our studies are aimed at bridging the gap between studies of neural development and analysis of the circuitry and function of the adult brain. The embryonic brain region that gives rise to the midbrain (mesencephalon) and anterior hindbrain (rhombomere 1) is an ideal model system for studying the genetic pathways that regulate the continuum of brain development and function. Anterior-posterior patterning of the mesencephalon and rhombomere 1 is orchestrated by an organizing center in the isthmus located between the two regions, whereas dorsal-ventral patterning is determined by Sonic hedgehog (Shh) expressed by the ventral floorplate. Fgf8 is the key isthmic organizer molecule, and acts by regulating the expression of genes such as Engrailed1 and 2.
One focus of our research is to determine how the mesencephalon and rhombomere 1, which gives rise to the cerebellum, are patterned in three dimensions over time. A second research focus is how the Engrailed genes regulate development of the cerebellum, a brain structure with a striking morphology consisting of folia separated by fissures of varying lengths. Underlying the folia, is a complex array of molecular codes consisting of parasagittal stripes of gene expression. Since the conserved pattern of folia and gene expression domains in mammals likely serves as a platform for organizing the sensory-motor circuits of the cerebellum, it is important to understand how such complex morphology and molecular coding arise. Our third area of research is understanding the degree to which resident stem cells in the adult brain, and other organs, can replenish damaged tissue or contribute to cancers. We are studying how the Shh signaling pathway regulates the behavior of adult stem cells through modifying the activity of the Gli transcription factors.
The Joyner laboratory studies mammalian brain development and the biology of adult stem cells using mouse as a model organism. Developmental mutants and alleles to mark and follow cells are created using sophisticated genetic approaches to study the ultimate function of genes in vivo and the fate of cells as they develop. These approaches are complemented by short term in vitro brain explant assays and electroporation experiments in chick embryos to rapidly compare the function of different proteins. Our three general areas of research are:
- Understanding how Fgf signaling from the isthmic organizer and Shh signaling from the floorplate regulate the earliest steps in formation of the midbrain and cerebellum.
- Elucidating the cellular and genetic events that regulate the formation of the conserved foliation pattern and molecular coding of the cerebellum, and how this influences formation of afferent and efferent cerebellum circuits.
- Determining the manner by which adult stem cells in the brain and epithelial organs are regulated by Shh/Gli signaling during homeostasis and in response to injury and cancer.
Address for correspondence:
1275 York Avenue, Box 511
New York, NY 10065
FedEx shipments or to reach lab:
Rockefeller Research Labs
Rm 701 (office)
Rm 721 (lab)
430 E. 67th Street
New York, NY 10065