Gary Gaufo and Anne Moon are studying the factors determining the differentiation of visceral and branchial motoneurons arising from the neural crest cells and ventral neural tube of rhombomere 4, respectively. These studies are based on the finding that motoneuron precursors of the pterygopalatine and submandibular gland arise from cells that are positive for Hoxb1, which is a marker for neural crest cells of rhombomere 4, and the requirement of early branchial motor neuron specification on Hoxb1. The former finding creates the opportunity to genetically track R4 neural crest cells throughout the course of their migration and differentiation, and to examine the differences between cells that differentiate into neurons rather than glia or other kinds of cells. The latter observation leads to question Hoxb1's possible role at later stages of differentiation. These experiments apply modern genetic methods to study one of the most basic of all neurobiological questions: the control and specification of neuronal differentiation.
Genetic fate map analysis identifies novel migration and differentiation of R4 NCCs. (A) E10.5 embryo showing rostral migration of R4-derived NCCs (green) into the first branchial arch and (A) roof of the oropharynx. (B, E). Hoxb1-derived NCCs (green) are associated with Tuj1-expressing nerve fibers (red). (C, F) Hoxb1-derived NCCs express the transcription factor Sox10, a Schwann cell determinant. By E11.5, Sox10-positive cells in the first branchial arch and roof of the oropharynx regions begin to express the transcription factor Phoxb, a autonomic motor neuron determinant.(H-K) Summary of the migration of R4-derived NCCs and their differentiation into postganglionic motor neurons of CNVII of the submandibular and pterygopalatine ganglia.
Transient expression of Hoxb1 in R4 neural crest cells (NCCs). (A) Lateral view of an E9.5 embryo expressing a Hoxb1-GFP reporter. (B) Transverse section of an E9.5 embryo immunolabeled for (B) Hoxb1 (green), (C) Hoxb1 (red) and Sox10 (green), and (D) Sox10 (green) and Phox2b (red). (E) Transverse section through R4 of E10.5 embryo immunolabled for Hoxb1 (red).
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