The Zimmerman Lab

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An initial step in nervous system development is the establishment of the mediolateral and anteroposterior axes. These axes subsequently serves as an information grid by which cells are instructed to differentiate to fates appropriate to their location. Our recent characterization of XASH-3, a Xenopus homolog of the Drosophila achaete-scute family of neural determination genes, indicates that regionalization along these axes is initiated at gastrula stages of development, well before the onset of neurulation. Using XASH-3 as well as other positional markers, we are examining the molecular signals that act to pattern gene expression along the mediolateral axis of the neuroectoderm at these early stages of development.

In addition, we are examining the role of regionally restricted genes, including XASH-3 and XATH-1, in the processes of neuronal specification and differentiation. As these genes are members of the bHLH family of transcription factors, they may act to translate positional information from the environment into a particular differentiation pathway within the cell. Over-expression assays suggest that both XASH-3 and XATH-1 drive neuronal differentiation within a subset of neural progenitors. Future studies are aimed at further understanding the molecular cascade of signals that leads from early stages of neural induction to the establishment of neuronal identity within the developing nervous system.

Mechanisms which influence mediolateral specification within the neuroectoderm.
Regionalized Gene Expression Along the Mediolateral Axisof the Neuroectoderm.

Establishing a molecular fate map of neuroectodermal progenitors.
Neural Progenitors at the Midpoint of the Dorsoventral Axis of the Spinal Cord.

Role of vertebrate homologs of Drosophila proneural genes, including XASH-3 and XATH-1, in neuronal specification and differentiation.

Ectopic XASH Expression Expands the Neural Domain within the Developing Embryo. | Ectopic XATH-1 Expression Drives Neuronal Differentiation Within the Non-Neuronal Ectoderm.

Kathryn Zimmerman, Assistant Professor

Ari Gershon, Biomedical Fellow

Peter Kim, Research Assistant

Johnson, J., Zimmerman, K., Saito, T., and Anderson, D. (1992) Induction and Repression of Mammalian Achaete-scute Homologue (MASH) Gene Expression During Neuronal Differentiation of P19 Embryonal Carcinoma Cells, Development, 114, 75-87. [Medline]

Zimmerman, K., Shih, J., Bars, J., Collazo, A., Anderson, D. (1993) XASH-3, a novel Xenopus achaete-scute homolog, provides an early marker of planar neural induction and position along the medio-lateral axis of the neural plate, Development, 119, 221-232. [Medline]

Ferreiro, B., Kintner, C., Zimmerman, K., Anderson, D., Harris, W. (1994) XASH genes promote neurogenesis in the vertebrate embryo, Development, 120, 3649-3655. [Medline]

Kim, P., Helms, A., Johnson, J., Zimmerman, K. XATH-1, a vertebrate homolog of Drosophila atonal, induces neuronal differentiation within non-neural ectodermal progenitors, submitted for publication.

For more information or questions or comments, Dr. Hatten is at hatten@rockvax.rockefeller.edu , and Dr. Zimmerman is at zimmerk@rockvax.rockefeller.edu