Defects in neural crest differentiation results in many human congenital birth defects. A better understanding of cell fate determination, migration, and differentiation of this population of cells during the formation of the craniofacial skeleton is an important step towards developing approaches to prevent and repair human neural crest associated birth defects. The objective of this proposal is to characterize the role of the transcription factor prdm1 in the differentiation of neural crest cells into the Craniofacial skeleton, prdm1 may promote specification of neural crest cells or alternatively, prdm1 may function later to promote the proliferation, migration, and differentiation of neural crest cells within the pharyngeal arches. Specifically, the hypothesis to be tested is that prdm1 is crucial for the proper induction of cranial neural crest derived tissues during pharyngeal arch differentiation. To test this, first it is necessary to determine the temporal and spatial requirement for prdm1 focusing on migration of cranial neural crest cells and later formation of the mature cartilage structures and this can be done using wild type and tg[fli1:GFP] zebrafish. To determine the effect of prdm1 on surrounding tissue, in situ hybridization of tissue specific genes will be analyzed. In addition, many genes have been identified as being required for craniofacial development and it will be important to determine how prdm1 interacts with these other required genes using mutant and rescue analysis. Finally, measuring proliferation and cell death in prdm1 mutants and tissue specific transplantation analysis between wild type and mutant neural crest cell populations will determine the function and the tissue specific requirement for prdm1 during Craniofacial development. Interactions between neural crest cells and surrounding tissues are crucial for normal pharyngeal arch and Craniofacial skeleton development and determining the role of the transcription factor prdm1 may help us to better understand the formation of Craniofacial structures and provide insight into preventing and treating these birth defects that arise from aberrant neural crest development, such as cleft lip and cleft palate.
|Jacobson, Saskia M; Birkholz, Denise A; McNamara, Marcy L et al. (2010) Subacute developmental exposure of zebrafish to the organophosphate pesticide metabolite, chlorpyrifos-oxon, results in defects in Rohon-Beard sensory neuron development. Aquat Toxicol 100:101-11|
|Birkholz, Denise A; Olesnicky Killian, Eugenia C; George, Kathleen M et al. (2009) Prdm1a is necessary for posterior pharyngeal arch development in zebrafish. Dev Dyn 238:2575-87|
|Olesnicky Killian, Eugenia C; Birkholz, Denise A; Artinger, Kristin Bruk (2009) A role for chemokine signaling in neural crest cell migration and craniofacial development. Dev Biol 333:161-72|