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1.  Expression of the bHLH transcription factor Tcf 12 (ME1) gene is linked to the expansion of precursor cell populations during neurogenesis⋆ 
In this study, we focused on the potential function of the murine gene Tcf 12 (also known as ME1 or HEB) encoding the bHLH E-protein ME1 during brain development. An exencephaly phenotype of low penetrance has consistently been observed in both Tcf 12 null mice and Tcf 12dm homozygous mice. Thus, to address the possible underlying mechanism of the Tcf 12 gene during the early steps of brain development, we performed a detailed analysis of its spatio-temporal expression pattern at distinct steps of gastrulation and neurogenesis. We found that Tcf 12 transcripts are detected in the embryonic ectoderm prior to neural induction during gastrulation. During neurulation, Tcf 12 transcripts are evident at high levels in the proliferating neuroepithelium of the neural folds and the cephalic mesenchyme. Thus, Tcf 12 gene expression coincides with the massive proliferation occurring in the forming neuroepithelium and cephalic mesenchyme during neural tube formation, which is consistent with the exencephaly phenotype of Tcf 12 null mice. In the developing cortex and spinal cord, Tcf 12 expression is restricted to the proliferative ventricular zones, indicating that Tcf 12 expression is down regulated when these neuronal cells undergo their final differentiation. Interestingly, we found that the postnatal Tcf 12 expression parallels the ongoing adult neurogenesis in the mitotically active subventricular zone. Thus, the timing and location of Tcf 12 expression combined with this severe neurulation defect support our hypothesis that the Tcf 12 gene may be involved in the control of proliferating neural stem cells and progenitor cells and that it may be critical to sustain their undifferentiated state during embryonic and adult neurogenesis.
PMCID: PMC2757747  PMID: 15018808
bHLH Transcription factor; E-protein; ME1; HEB; Stem cell; Progenitor cell; Gastrulation; Neural tube formation; Proliferation; Postnatal neurogenesis; Subventricular zone

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