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Taste system of vertebrates during embryogenesis
Work in our lab focuses on neural development. We use the taste system, one of our 5 basic senses, as a model to investigate how the peripheral nervous system forms during embryogenesis. In particular, our research focuses on the development of taste buds in the mouth, and of the sensory neurons of the cranial nerves that convey taste information from taste buds to specific relay nuclei of the hindbrain. These 3 components, taste buds, sensory neurons, and the hindbrain, each form independently and at some distance from one another in early embryos. Importantly, their development becomes coordinated to generate a connected and fully functional taste system by birth, enabling newborns to ingest the right foods and reject the wrong ones. Postnatally, and throughout adult life, the cells within taste buds are continually replaced, and thus this process must also occur reliably so that our sense of taste is not interrupted. Moreover, taste function has been increasingly linked to human health, in that variability in taste sensation correlates with, and may in part be causal for, major health problems, including cardiovascular disease and obesity. Specifically we are interested in the following questions:
To study the taste system, we use both mice and an aquatic salamander, the axolotl. Each type of animal has distinct advantages for our studies. We use axolotl embryos to rapidly test hypotheses of tissue-level, cellular and molecular mechanisms governing taste system development. Axolotl embryos are large, and their development is rapid and external, facilitating microsurgical manipulation, microinjection, and targeted electroporation at virtually any stage of development. We can then assess the impact of early alterations in cellular and molecular signaling on the subsequent development of taste buds and their innervation. For example, using microsurgical grafting approaches and explant culture, we have found that taste bud development is intrinsic to the oral epithelium, depends upon intercellular communication within that epithelium during an early critical period, and is set in motion even earlier in development by signals from the notochord during gastrulation. In terms of the taste sensory neurons, we have found that when these cells are raised in culture, their axons grow preferentially toward, and are maintained only by, their appropriate taste bud targets. And most recently, we have taken advantage of a newly generated line of axolotls which express GFP in all cells, to identify the embryonic origin of the sensory neurons that innervate taste buds. We are continuing several studies in axolotls, including: investigating the signals the notochord uses to trigger taste bud development in the endodermal epithelium, assessing the molecular mechanisms involved in taste organ patterning during the critical period, and exploring the role of specific neurotrophic factors in development of the taste sensory neurons. The majority of current work in our lab focuses on the taste system of mice. In particular, we are now making full use of powerful molecular genetic approaches available in this model system to investigate the cellular and molecular mechanisms regulating embryonic development of taste buds and their innervation, and more recently, have begun to explore molecular regulation of mature taste buds. Using tissue-specific and inducible Cre-lox mouse lines, we have shown that the Wnt/ß-catenin pathway is required as an early initiator for taste bud formations, acting upstream of other known regulators, including Sonic Hedgehog (Shh) and Bone Morphogenetic Protein (BMP)-4. We have also implicated the Notch pathway, based upon gene expression patterns, in taste organ development, although we have yet to demonstrate a functional requirement for these genes. In sum, we predict that by employing a dual species approach, using the unique advantages offered by each species, that we will come to understand the conserved cellular and molecular mechanisms that govern development of this key sensory system. Selected Publications
Harlow DE, Barlow LA. Embryonic origin of gustatory cranial sensory neurons. Dev Biol. 2007 Aug 15; [Epub ahead of print] Liu, F., S.Thirumangalathu, N.M. Gallant, C.L. Stoick-Cooper, S.H. Yang, S.T. Reddy, T. Andl, M.M. Taketo, A.A. Dlugosz, R.T. Moon, L.A. Barlow* and S.E. Millar*. 2007. Wnt-ß-catenin signaling initiates taste papilla development. *co-corresponding authors. Nature Genetics. 39:106-12. Seta, Y., C.L. Stoick-Cooper, T. Toyono, S. Kataoka, K. Toyoshima and L.A. Barlow. 2006. The bHLH transcription factors, Hes6, and Mash1, are expressed in distinct subsets of cells within adult taste buds. Arch Histol. Cytol. 69(3):189-198. Parker, M.A., M. Bell and L.A. Barlow. 2004. Cell contact-dependent mechanisms specify taste bud number and size during a critical period early in embryonic development. Dev. Dynamics 230:630-642. Gross, J.B, A. Gottlieb and L.A. Barlow.;2003. Gustatory neurons derived from epibranchial placodes are attracted to, and trophically supported by taste bud-bearing endoderm in vitro. Dev Biol. 264:467-481. Seta, Y., C. Seta and L.A. Barlow. 2003. Notch-associated gene expression in embryonic and adult taste papillae and taste buds suggests a role in taste cell lineage decisions. J Comp Neurol 464:49-61. Barlow, L.A. 2001. Specification of pharyngeal endoderm is dependent on early signals from axial mesoderm. Development 128(2): 4573-4583. |
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