The cAMP pathway is a necessary inductive signal in sympathoadrenal (SA) cell development
Abstract
In primary neural crest cultures, the cAMP signaling pathway modulates both positive and negative signals influencing the development of SympathoAdrenal lineage (SA) cells. However, the mechanism by which cAMP acts as a rheostat of SA cell differentiation remains to be determined. Specifically, moderate activation of CAMP signaling promotes, in synergy with BMP2, SA cell development and the transcription of the SA lineage-determining gene Phox2a. Herein, evidence is provided that all the cAMP signaling components participate in the synergistic interaction with the BMP2 pathway in effecting SA cell development. Utilizing avian retroviral constructs, including A-CREB (dominant negative CREB), E1A and ΔE1A (a CBP interfering protein and its inactive control respectively), the role of both CBP and CREB is demonstrated in SA cell development. In addition, use of the constitutively active CREBDIEDML enabled the identification of the requirement of PKA activation in the process of SA cell development, by monitoring the expression of the proneural gene phox2a and the SA cell differentiation marker, tyrosine hydroxylase (TH). Specifically, PKA activation mediates the activation of a ser/thr phosphatase, protein phosphatase 2A (PP2A), required for activation of the proneural phox2 transcription factors. Analyses of the effect of A-CREB, CREBDIEDML, E1A and ΔE1A by clonal assays demonstrate that they do not alter neural crest cell survival, supporting that these cAMP signaling components, CREB, CBP and PKA, play an inductive role in promoting the development of neural crest cells into the SA lineage cells. This study identified, for the first time, the inductive role of the cAMP pathway in SA cell development.
Degree
Ph.D.
Advisors
Andrisani, Purdue University.
Subject Area
Neurology
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