Adenovirus-mediated ectopic expression of Msx2 in even-numbered rhombomeres induces apoptotic elimination of cranial neural crest cells in ovo

• Published in: Development (Cambridge) Vol. 125; no. 9; pp. 1627 - 1635
• Main Authors: Takahashi, K, Nuckolls, G H, Tanaka, O, Semba, I, Takahashi, I, Dashner, R, Shum, L, Slavkin, H C
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 01.05.1998
• Subjects: Adenoviridae - genetics; Animals; Apoptosis - physiology; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins - pharmacology; Cell Movement; Chick Embryo; Culture Techniques; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Epithelium; Gene Expression; Gene Transfer Techniques; Genetic Vectors; Homeodomain Proteins; Humans; Mice; Middle Aged; Neural Crest - cytology; Neural Crest - embryology; Rhombencephalon - cytology; Rhombencephalon - embryology; Skull
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.125.9.1627

Distinct cranial neural crest-derived cell types (a number of neuronal as well as non-neuronal cell lineages) are generated at characteristic times and positions in the rhombomeres of the hindbrain in developing vertebrate embryos. To examine this developmental process, we developed a novel strategy designed to test the efficacy of gain-of-function Msx2 expression within rhombomeres in ovo prior to the emigration of cranial neural crest cells (CNCC). Previous studies indicate that CNCC from odd-numbered rhombomeres (r3 and r5) undergo apoptosis in response to exogenous BMP4. We provide evidence that targeted infection in ovo using adenovirus containing Msx2 and a reporter molecule indicative of translation can induce apoptosis in either even- or odd-numbered rhombomeres. Furthermore, infected lacZ-control explants indicated that CNCC emigrated, and that 20% of these cells were double positive for crest cell markers HNK-1 and beta-gal. In contrast, there were no HNK-1 and Msx2 double positive cells emigrating from Msx2 infected explants. These results support the hypothesis that apoptotic elimination of CNCC can be induced by ‘gain-of-function’ Msx2 expression in even-numbered rhombomeres. These inductive interactions involve qualitative, quantitative, positional and temporal differences in TGF-beta-related signals, Msx2 expression and other transcriptional control.