In vertebrates, as in other animals, the ectoderm has two primary fates, epidermis and central nervous system (CNS). The goal of this project is to understand the mechanisms that determine how ectodermal cells choose between these two pathways, and how the ensuing tissue patterning and differentiation are regulated. It has been well established that signaling by bone morphogenetic proteins (BMPs) is the primary event that initiates epidermal development in the amphibian embryo. The experimental approach taken by this laboratory has been to use dependence upon such signaling as a criterion for identifying genes that may regulate the epidermal/neural developmental program. Attention has been focused on the Distal-less homologs Dlx3, 5 and 6 and on the transcriptional activator AP-2. Additional genes are being sought using subtractive hybridization/microarray techniques. We have found that the three Dlx genes are differentially regulated by a graded response to BMP signaling, and that this can account for at least some of the major features of the spatial pattern of Dlx gene expression in the gastrula. Dlx3 appears to be involved in establishing the lateral boundary of cranial neural crest induction, in a manner similar to the anti-neural properties we previously discovered for this gene. Interestingly, this inhibitory function does not appear to involve direct regulation of transcription by Dlx3, but is more likely dependent upon protein-protein interactions. The roles of Dlx5 and Dlx6 remain obscure, but the possibility that this subfamily of homeobox genes function to interpret a morphogenetic gradient in the embryo is very intriguing. The findings that AP2 expression is BMP-dependent, and that over-expression of this factor can rescue epidermal gene activity in BMP-disabled ectoderm are also highly interesting, as this gene was identified by our laboratory several years ago as a potential epidermal regulatory factor, using a promoter analysis approach. In the coming year, the lab will focus primarily on investigating the function of AP-2 in regulating epidermal and neural crest differentiation, and on transgenic and proteomic approaches to Dlx gene function in ectodermal pattern formation.

Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2001
Total Cost
Indirect Cost
Name
U.S. National Inst/Child Hlth/Human Dev
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Yamazaki, Akio; Nishizawa, Yuji; Matsuura, Isao et al. (2013) Microtubule-associated protein tau in bovine retinal photoreceptor rod outer segments: comparison with brain tau. Biochim Biophys Acta 1832:1549-59
Luo, Ting; Xu, Yanhua; Hoffman, Trevor L et al. (2007) Inca: a novel p21-activated kinase-associated protein required for cranial neural crest development. Development 134:1279-89
Rangarajan, Janaki; Luo, Ting; Sargent, Thomas D (2006) PCNS: a novel protocadherin required for cranial neural crest migration and somite morphogenesis in Xenopus. Dev Biol 295:206-18
Khadka, Deepak; Luo, Ting; Sargent, Thomas D (2006) Msx1 and Msx2 have shared essential functions in neural crest but may be dispensable in epidermis and axis formation in Xenopus. Int J Dev Biol 50:499-502
Zhang, Yanhui; Luo, Ting; Sargent, Thomas D (2006) Expression of TFAP2beta and TFAP2gamma genes in Xenopus laevis. Gene Expr Patterns 6:589-95
Sargent, Thomas D (2006) Transcriptional regulation at the neural plate border. Adv Exp Med Biol 589:32-44
Lim, Jae H; Booker, Anne B; Luo, Ting et al. (2005) AP-2alpha selectively regulates fragile X mental retardation-1 gene transcription during embryonic development. Hum Mol Genet 14:2027-34
Lim, Jae H; Luo, Ting; Sargent, Thomas D et al. (2005) Developmental expression of Xenopus fragile X mental retardation-1 gene. Int J Dev Biol 49:981-4
Luo, Ting; Zhang, Yanhui; Khadka, Deepak et al. (2005) Regulatory targets for transcription factor AP2 in Xenopus embryos. Dev Growth Differ 47:403-13
Saint-Germain, Natasha; Lee, Young-Hoon; Zhang, Yanhui et al. (2004) Specification of the otic placode depends on Sox9 function in Xenopus. Development 131:1755-63

Showing the most recent 10 out of 18 publications