Neurogenin2 expression together with NeuroM regulates GDNF family neurotrophic factor receptor alpha 1 (GFR alpha 1) expression in the embryonic spinal cord

作者：Shimoda Takako; Yaginuma Hiroyuki; Sato Noboru; Homma Shunsaku^*

来源：Developmental Biology, 2012, 370(2): 250-263.

DOI：10.1016/j.ydbio.2012.08.002

• Math3
• NeuroD4
• Cash1
• Ptf1a
• p27
• Chick
• Electroporation
• In situ hybridization

In many regions of the nervous system, the combinatorial action of transcriptional factors specifies the individual fate of neuronal subtypes. Contrary to this, we report that a single transcriptional factor controls a phenotype shared by different subtypes of neurons, namely the expression of a neurotrophic factor receptor in the spinal cord. Along the dorsoventral axis of the chick embryo spinal cord, the expression pattern of a specific receptor for glial cell line derived-neurotrophic factor (GDNF family of receptors alpha 1: GFR alpha 1) was related to that of two basic helix-loop-helix (bHLH) transcriptional factors (NeuroM and Neurogenin2: Ngn2). In ovo electroporation in the chick embryo revealed that the overexpression of NeuroM alone was sufficient to induce ectopic GFR alpha 1 expression without overt neuronal differentiation, whereas the suppression of NeuroM activity resulted in the specific loss of GFR alpha 1 expression, indicating that NeuroM may act as a differentiation factor for GFR alpha 1 expression. Ngn2 overexpression was also sufficient to induce precocious GFR alpha 1 expression. However, the forced expression of both obligate suppressor and activator forms of Ngn2 also induced aberrant GFR alpha 1 expression. Thus, any deviation from an optimum level of Ngn2 expression resulted in aberrant GFR alpha 1 expression. Consistent with this, manipulation of Ngn2 expression levels by other bHLH factors also resulted in ectopic GFR alpha 1 expression. For example, the downregulation by Ascl1 and the upregulation by Ptf1a induced ectopic GFR alpha 1 expression, irrespective of endogenous expression patterns of Ascl1 and Ptf1a (Ascl1/Ptf1) in the spinal cord. The suppression of Ascl1/Ptf1a activities abolished Ngn2 and GFR alpha 1 expression, even in Ascl1/Ptf1a-negative regions. These data indicate the presence of a distinct regulatory sequence for a determinant of GFR alpha 1 expression, in which Ascl1/Ptf1a may competitively intervene to stochastically modulate default Ngn2 expression levels. Thus, Ngn2 together with NeuroM serves as readout to regulate GFR alpha 1 expression, which occurs in multiple subtypes of spinal neurons.

• 出版日期2012-10-15