Cerebellum (2010) 9:537–547 Fig. 2. Myc cerebellar knock- out phenotypes. a Sagittal sections from control and DKO embryonic cerebella (E17.5) or b cerebella from pups (P6) stained with Nissl. Scale bars=100 μM in (a) and in (b) 500 μM A B E17.5 Control Control P6 DKO 541 DKO myc Family Expression Patterns in the Embryonic Brain Correlate with the General Domain Specificity of myc Knockout Phenotypes We have previously observed high levels of N-Myc protein expression in the developing cortex and cerebella [16]. These findings correlated with myc family expression data at E15.5 from the brain gene expression website: http://www.stjudebgem.org/web/mainPage/mainPage.php. While c-myc expression at the protein or RNA levels is difficult to detect, there are hints of low-level expression in a number of regions including the developing cortex. N- myc is fairly ubiquitously expressed, but with relatively lower or absent expression in some midbrain regions and very high levels in the neocortex and the EGL. L-myc, despite no reported KO phenotype, has very high expression in the VZ of the embryonic midbrain, as well as moderate levels in the developing cerebellum and cortex. A Lack of c- and N-myc Almost Completely Ablates Cerebellar Development from P6-P21 To explore the effects of the myc DKO on cerebellar development further, we examined the mature DKO cerebellum. Between P6 and P21, the DKO cerebellum grew little and there remained only one possible folium, hardly recognizable as such. Reflective of little post-natal cerebellar change in the DKO, a putative, residual EGL was evident in the P21 DKO by DAPI staining (Fig. 3 blue arrows). Staining of the DKO with NeuN, which highlights cerebellar granule neurons, indicated an absence of the internal granule cell layer (IGL) with a scattered pattern of very few of granule neurons, abnormally intense NeuN nuclear staining and possible reductions in nuclear size (Fig. 3a). The astroglia and oligodendrocytes that normally are present within the granule cell layer are ectopic and disorganized in the DKO (Fig. 3a, b), with an overrepre- sentation of astroglia and abnormal oligodendrocyte