Suppression

 

How Is Suppression Involved in Neural Development?

Suppression is a key mechanism in neural development because all ectoderm has the capability of differentiating into neural ectoderm. Thus, non-neural and pre-neural ectoderm are under constant suppression of their neural characteristics. In order for neural tissue to develop properly, this suppression must somehow be turned off. This page describes three examples of suppression in neural development.

Wnt1 Gene

The Wnt1 gene arises in a critical role in the differentiation of embryonic ectodermal cells in the chick model. Neural tissue is induced to form from ectodermal cells when the activity of bone morphogenic protein (BMP) is halted and bFGF signals the tissue to begin it’s transformation. The expression of Wnt1 is critical because it blocks the response of epiblast cells to bFGF. Future neural tissue cells must have the Wnt1 signal turned off to allow induction by bFGF. (26)

 

(26)

 Proposed signalling pathway for neural induction in the chick embryo. a, Medial epiblast cells express FGFs but not Wnts. FGF signalling is shown to activate two distinct transduction pathways in epiblast cells: (1) repression of Bmp expression and prevention of BMP signalling (solid line from FGF), and (2) the promotion of a neural fate by a pathway independent of the repression of Bmp expression is required for the progression to a neural fate (dashed line from FGF). b, Lateral epiblast cells express FGFs and Wnts. Wnt signalling blocks the response of epiblast cells to FGFs, and thus Bmp genes are expressed. BMP signalling promotes epidermal fate and represses Fgf expression. Exposure to low concentrations of Wnts blocks the ability of FGFs to repress Bmp expression, but the independent pathway involved in promotion of neural fate is preserved. Thus, BMP antagonists can restore neural fate. High concentrations of Wnts block both FGF-dependent pathways, and thus BMP antagonists do not restore neural fate. (caption from source)

 

Neuron-Restrictive Silencer Factor

The protein neuron-restrictive silencer factor (NRSF) is expressed in undifferentiated CNS neural progenitors but not in mature neurons. This protein was found to be a master regulator of neuronal determination and differentiation of CNS stem cells. Neuron-specific gene expression is controlled primarily by selective silencing. This process differs in the rest of the body, where genes are turned on to signal the differentiation of certain tissues. NRSF is also found in non-neural tissues, where it acts as a negative regulator for neuron-specific genes. (28)

 

(27)

Neighbor Cells Help End Suppression

TH+ cells can also be induced by stromal cell-derived inducing activity (SDIA). This induction has been observed in both mouse and primate ES cells. Noggin and Chordin are good examples of SDIA (am I comprehending the idea of SDIActivity correctly?). These proteins bind to and inactivate BMP, another protein which happens to suppress neural differentiation in the ectoderm and promotes epidermal differentiation. (27)

 
Neural differentiation of monkey ES cells by SDIA. (A) Phase contrast image of an undifferentiated ES cell colony. (B and C) Alkaline phosphatase (ALP) staining and SSEA-4 immunostaining of undifferentiated ES cell colonies, respectively. Arrows indicate colonies of ES cells. Surrounding cells are feeder cells (mouse embryonic fibroblasts). (D) SDIA-treated ES colonies stained with anti-NCAM antibody. (E) SDIA-induced neurons double-stained with anti-NeuN (green) and TuJ (red) antibodies (high magnification view). (F) Suppression of neuronal differentiation by BMP4 and serum. Serum (instead of knockout serum replacement) was used in the differentiation medium. (caption from source)  
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