Development of the mammalian nervous system rests on genetic programs that are executed by gene transcription factors in neuronal and glial cells. This line of research focusses on regulatory genes that encode neuronal basic helix-loop-helix (bHLH) transcription factors NEX (Math2), NeuroD (BETA2), and NDRF (NeuroD2), which are co-expressed in projection neurons of the developing and adult cortex (Schwab et al., 1998).
Null mutations of individual neuronal bHLH proteins lack obvious neocortical defects (Schwab et al., 2000; Goebbels et al., 2006) suggesting functional redundancy. In contrast, fiber tracts of neocortical origin are massively reduced or completely absent in NEX/NDRF double mutants, demonstrating that neocortical projection neurons require transcriptional specification by neuronal bHLH proteins to execute an intrinsic program of long-range cortical connectivity.
Deficiency of neuronal bHLH transcription factors NEX and NDRF in double mutant mice (DKO) impairs growth of callosal axons (marked by green fluorescence) towards the midline resulting in corpus callosum (CC) agenesis. Scalebar, 250 µm. (Bormuth et al., submitted)
To study cortical bHLH functions in the mature brain, we have generated several mouse lines that permit genetic manipulations in adult mice, including conditional NeuroD mutants (Goebbels et al., 2005). Taking advantage of these mouse lines, we are currently addressing the question whether these proteins are required not only for brain development, but also for neuronal plasticity and structural changes in the mature brain that have been associated with learning and long-term memory.
Victor Tarabykin/Ingo Bormuth, Göttingen
Weiqi Zhang, Münster