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The Dorsal Aorta Initiates a Molecular Cascade That Instructs Sympatho-Adrenal Specification

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Science  22 Jun 2012:
Vol. 336, Issue 6088, pp. 1578-1581
DOI: 10.1126/science.1222369

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Master Regulator

Sympathetic neurons and the adrenal medulla are part of the autonomic nervous system, which is important in the control of a variety of bodily functions and in responses to stress. Interactions between the nervous system and the vascular system have been poorly explored. During development, sympathetic neurons and adrenal medulla cells are derived from the same precursors—neural crest cells—embryonic cohorts that undergo massive migration in the body. Using blood vessel–specific gene manipulation in chicken embryos, Saito et al. (p. 1578) revealed a role for the dorsal aorta in regulating the early migration of neural crest cells and later in development on the segregation of adrenal medulla and sympathetic neurons. The dorsal aorta expresses multiple soluble morphogenetic and growth factors that regulate complex morphogenesis in a spatiotemporal manner. Furthermore, in mice, the morphogenesis of the adrenal medulla was controlled both by the aorta and the adrenal cortex.

Abstract

The autonomic nervous system, which includes the sympathetic neurons and adrenal medulla, originates from the neural crest. Combining avian blood vessel–specific gene manipulation and mouse genetics, we addressed a long-standing question of how neural crest cells (NCCs) generate sympathetic and medullary lineages during embryogenesis. We found that the dorsal aorta acts as a morphogenetic signaling center that coordinates NCC migration and cell lineage segregation. Bone morphogenetic proteins (BMPs) produced by the dorsal aorta are critical for the production of the chemokine stromal cell–derived factor–1 (SDF -1) and Neuregulin 1 in the para-aortic region, which act as chemoattractants for early migration. Later, BMP signaling is directly involved in the sympatho-medullary segregation. This study provides insights into the complex developmental signaling cascade that instructs one of the earliest events of neurovascular interactions guiding embryonic development.

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