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Research at Mass General
The goal of my lab is to understand the molecular genetics of appendage formation in vertebrates.
The focus of my research is on the process by which competent cells are allocated to distinct fates in appropriate numbers and positions to generate organized structures. We have developed the chick feather field as a system to study the molecular genetics of this process in vivo and in vitro.
The relatively simple yet highly organized pattern of feather buds is an experimentally tractable system to study the interactions between intercellular signaling pathways that specify organizing centers and mediate their activity. We have divided the process of pattern formation in the feather field to a series of discrete steps with molecular markers to identify them.
In this way, we can untangle the interactions between multiple signaling pathways in a single event and then reconstruct the sequential roles of each pathway in the ultimate generation of a feather tract. We have identified roles for Sonic hedgehog, BMPs, FGFs, Wnts and the Notch signaling pathway and are studying interactions between these pathways to generate pattern during tract morphogenesis.
To complement the analysis of gene function in intact tissues, we have developed methods to purify specific cell populations in the hair follicle using transgenic mice expressing fluorescent proteins under the control of cell type specific promoters.
This allows us to take advantage of whole genome approaches to identify new signals involved in cell- cell interactions in the follicle and to dissect specific inductive interactions. This work has confirmed the similarity between follicle formation in mouse and chick embryos and follicle regeneration in the adult and we continue to move between these experimental systems to test the function of candidate genes.
Another aspect of the pattern formation process is the restriction of potential in muli-potent cells as development proceeds.
A second focus of research in the lab is on the role of the Ikaros family of transcription factors on the specification of cell potential.
We hope to discern the manner in which alterations in the nucleus of the cell contribute to the changing response to extrinsic signals which is an integral part of pattern formation.
We have cloned three additional genes, which with Ikaros make up the Ikaros gene family. We use gain and loss of function experiments in mice, chicks and frogs to analyze their roles in specific lineages.
1. Kelley C, Ikeda T, Avitahl N, Koipally J, Georgopoulos K, Morgan BA. Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors. Current Biology 1998; 8:508-515.
2. Noramly S, Morgan BA. BMPs mediate lateral inhibition at successive stages in feather tract development. Development 1998; 125:3775-3787.
3. Wang J, Avitahl N, Friedrich C, Ikeda T, Renold A, Andrikopouolos K, Morgan BA, Georgopouolos K. Aiolos regulates B cell activation and maturation to effector state. Immunity 1998; 9:543-553.
4. Noramly S, Freeman A, Morgan BA. Beta-catenin signaling can initiate feather bud development. Development 1999; 126:3509-3521.
5. Kishimoto J, Burgeson R, Morgan BA. Wnt signaling maintains the hair inducing activity of the dermal papilla. Genes & Dev. 2000; 14:1181-1185.
6. Dohrmann C, Noramly S, Raftery L, Morgan BA. Opposing effects on TSC-22 expression by BMP and receptor tyrosine kinase signals in the developing feather tract. Dev. Dynamics 2002; 223:85-95.
7. Houghton L, Freeman A, Morgan B. Expression and Regulation of Groucho Related Genes in Embryonic Chicken Feather Bud. Developmental Dynamics 2003; 226(4):587-595.
8. Shimizu H and Morgan B. Wnt Signaling through the B-Catenin pathway is sufficient to maintain, but not restore, hair growth promoting activity of dermal cells. Journal of Invest. Derm. 2004; 122(2):239-245.
9. Houghton L, Lindon C, and Morgan BA. The ectodysplasin pathway in feather tract development. Development 2005; 132: 863-872.
10. Levy V, Lindon, C, Harfe B, and Morgan BA. Distinct stem cell populations regenerate the follicle and interfollicular epidermis. Dev. Cell 2005; 9(6) 855-861.
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