ABSTRACT
Multiple tissue interactions and signaling within the pharyngeal arches are required for development of the craniofacial skeleton. Here, we focus on the role of the transcription factor prdm1a in the differentiation of the posterior skeleton. prdm1a is expressed in the presumptive pharyngeal arch region and later in an endodermal pouch, the otic vesicle, and pharyngeal teeth. prdm1a mutants display a reduction in pharyngeal arch markers, a loss of posterior ceratobranchial cartilages, and a reduction in most neural crest-derived dermal bones. This is likely caused by a decrease in the number of proliferating cells but not an increase in cell death. Finally, a reduction in two key developmental signaling pathways, Fgf and retinoic acid, alters prdm1a expression, suggesting that prdm1a expression is mediated by these signaling pathways to pattern the posterior craniofacial skeleton. Together, these results indicate an essential role for prdm1a in the development of the zebrafish craniofacial skeleton.
Subject(s)
Branchial Region/embryology , DNA-Binding Proteins/metabolism , Embryo, Nonmammalian , Morphogenesis/physiology , Nuclear Proteins/metabolism , Zebrafish Proteins/metabolism , Zebrafish/anatomy & histology , Zebrafish/embryology , Animals , Biomarkers/metabolism , Branchial Region/anatomy & histology , Cartilage/cytology , Cartilage/metabolism , Cell Proliferation , DNA-Binding Proteins/genetics , Embryo, Nonmammalian/anatomy & histology , Embryo, Nonmammalian/metabolism , Facial Bones/abnormalities , Facial Bones/anatomy & histology , Facial Bones/embryology , Fibroblast Growth Factors/metabolism , Gene Expression Regulation, Developmental , Humans , Mice , Nuclear Proteins/genetics , Positive Regulatory Domain I-Binding Factor 1 , Signal Transduction/physiology , Skull/abnormalities , Skull/anatomy & histology , Skull/embryology , Tretinoin/metabolism , Zebrafish/genetics , Zebrafish/metabolism , Zebrafish Proteins/geneticsABSTRACT
Neural crest cells (NCCs) are a unique population of multipotent cells that migrate along defined pathways throughout the embryo and give rise to many diverse cell types including pigment cells, craniofacial cartilage and the peripheral nervous system (PNS). Aberrant migration of NCCs results in a wide variety of congenital birth defects including craniofacial abnormalities. The chemokine Sdf1 and its receptors, Cxcr4 and Cxcr7, have been identified as key components in the regulation of cell migration in a variety of tissues. Here we describe a novel role for the zebrafish chemokine receptor Cxcr4a in the development and migration of cranial NCCs (CNCCs). We find that loss of Cxcr4a, but not Cxcr7b, results in aberrant CNCC migration defects in the neurocranium, as well as cranial ganglia dysmorphogenesis. Moreover, overexpression of either Sdf1b or Cxcr4a causes aberrant CNCC migration and results in ectopic craniofacial cartilages. We propose a model in which Sdf1b signaling from the pharyngeal arch endoderm and optic stalk to Cxcr4a expressing CNCCs is important for both the proper condensation of the CNCCs into pharyngeal arches and the subsequent patterning and morphogenesis of the neural crest derived tissues.
