Studies of the Tissues and Molecules That Regulate the Migration of Cranial Neural Crest Cells in the Chicken Embryo: Roles of Midline 1 and Retinoic Acid

Latta, Elizabeth Jane (2010). Studies of the Tissues and Molecules That Regulate the Migration of Cranial Neural Crest Cells in the Chicken Embryo: Roles of Midline 1 and Retinoic Acid. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000f238

Abstract

Cranial neural crest cells (cNCC) emigrate from the neuroepithelium to form the cartilaginous structures of the face and much of the peripheral nervous system of the head. Several genetic disorders and drug compounds can disrupt the patterning of cNCC-derived tissues during development.

I have studied cNCC patterning in the chick embryo, focussing on one genetic disorder (X-linked Opitz syndrome, caused by mutations in the MIDLINE1 (MID1) gene) and one drug compound (retinoic acid).

I demonstrate the expression pattern of the chick orthologue of MID1 and show that the Mid1 protein, via its effects on Protein Phosphatase 2A, controls the migration of cNCCs and regulates the timing of cranial gangliogenesis, likely by altering cNCC protease activities.

Retinoic Acid (RA) is a diffusible morphogen and well-known teratogen that causes patterning defects in cNCC migration. I provide evidence that the cranial mesenchyme adjacent to rhombomere 3 of the hindbrain is a potent responder to the presence of RA, resulting in cNCC mis-migration. Furthermore, I demonstrate that the 9-cis RA isoform is more potent than the all-trans RA isoform at causing cNCC mis-migration.

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