Faculty Member - Division of Biological Sciences University of Missouri-Columbia

Detection of Gbx1 and Gbx2 RNA expression in wild-type embryos at embryonic day 10.5 by whole-mount in situ hybridization. (A,B) are lateral views. (C,D) are transverse sections of the neural tube. ba, branchial arch; fl, forelimb bud; g, genital region; hl, hindlimb bud.

Research description

To understand normal brain/central nervous system (CNS) function and neuropathies affecting the CNS, it is paramount to understand how nerve cells are assembled into neural circuits that define the behavioral repertoire of the mature organism. Locomotion in mammals is generally thought to depend on neuronal circuits in the spinal cord. Therefore, the study of movement control has relevance to our general understanding of brain function, by providing important clues about the assembly of neuronal circuits that underlie complex behaviors. The main research interest in my laboratory is to understand the developmental program of nerve cells within the mouse embryonic spinal cord. The mouse embryonic spinal cord contains multipotential progenitor cells, which give rise to postmitotic interneurons and motorneurons. Because of its relative simplicity, the developing spinal cord serves as an important system for defining molecular mechanisms that contribute to the assembly of neural circuits.

Currently, our research focuses on a class of homeobox genes, known as the Gbx genes, which encode DNA-binding transcription factors expressed in the developing CNS. Developmental and functional studies addressing neuronal patterning in the mouse embryonic spinal cord have highlighted the central role of homeoproteins in controlling the expression of genes in neural progenitor cells and ultimately their specification, differentiation and assembly into functional circuits. We have recently shown that the Gbx gene family is involved in regulating anterioposterior patterning of the anterior hindbrain, branchiomotor neuron development and locomotion. We are particularly interested in understanding: 1) how these transcription factors confer positional value of nerve cells; 2) how they promote the specification of nerve cell identity; and 3) the identity of the transcriptional target genes that are directly regulated by them in vivo.

A major experimental approach utilized in the lab is to study the disruption of normal development in mouse embryos that carry loss-of-function alleles generated by Cre-loxP and Flp-FRT-mediated DNA recombination. This methodology has proved extremely advantageous by enabling high fidelity DNA modifications and the precise control of gene expression in a tissue-specific manner. By using this methodology in combination with other molecular and histological techniques, we aim to provide valuable insight towards understanding the assembly of functional circuits in the developing spinal cord and the interneuronal network underlying locomotion in mammals. Detection of Gbx1 and Gbx2 RNA expression in wild-type embryos at embryonic day 10.5 by whole-mount in situ hybridization. (A,B) are lateral views. (C,D) are transverse sections of the neural tube. ba, branchial arch; fl, forelimb bud; g, genital region; hl, hindlimb bud.

Selected publications

Waters, S. T. and M. Lewandoski. 2006. A threshold requirement for Gbx2 levels in hindbrain development. Development 133: 1991-2000.

Waters, S. T., Wilson, C. P. and M. Lewandoski. 2003. Cloning and embryonic expression analysis of the mouse Gbx1 gene. Gene Expression Patterns 3: 313-317.