Furthermore, in view of the relevance of FMR2 and LAF4 to neurodevelopmental disease and cerebellar neurodegeneration in the Af4 mutant mouse robotic, the role of AFF Axitinib 319460-85-0 proteins in the CNS warrants further investigation. For example, specific temporal patterns of Fmr2 and Laf4 expression have been described in the developing mouse embryo; whereas Fmr2 expression peaks at late embryonic stages, Laf4 was shown to be expressed in the developing cortex as early as embryonic day 13.5. At E13.5, Laf4 is also detected in cartilage tissue in different regions of the embryo as well as in the lung, kidney tubules and bladder. A similar pattern has been confirmed in humans, with very high levels of LAF4 seen in the fetal brain, which then diminished to much lower levels in adults. In light of the reported human LAF4 deletion, association with ID and known expression patterns, the aim of this study was to further investigate the function of Laf4 in the brain, focusing on the role of the protein in the developing cortex. By manipulating expression levels of Laf4 by whole embryo electroporation followed by organotypic culture experiments, we discovered that Laf4 is required for cortical cell migration. We then went on to examine the potential targets of Laf4 transcriptional control and found that Laf4 regulates the expression of Mdga2, an important structural protein in the developing CNS. These data represent the first detailed functional studies of Laf4 and highlight the importance of the gene in the developing nervous system with relevance to human neurodevelopmental disorders. Although AF4, AF5Q31 and LAF4 are highly expressed in human embryonic brains, a functional role for these genes during neurodevelopment has not been described. We showed here that Laf4 is expressed as early as E13.5 in the mouse neocortex and demonstrated a direct function for this gene in migration of cortical neurons. It is noteworthy that the AFF genes Fmr2 and Af4 are also expressed in the mouse cortical plate, but later in development than Laf4, suggesting that Laf4 may have a specific and unique role at the earlier embryonic timepoints studied here. Given the degree of sequence conservation within the ALF family, our present study potentially has implications for AFF-associated disorders of the CNS such as FRAXE mental retardation associated with FMR2. Interestingly, Fmr2 knockout mice show a very mild phenotype, displaying memory impairment and abnormalities in nociception. While no cortical migration deficits have been noted in these mice, no detailed anatomical analysis was described. However, more recently Fmr2 has been shown to regulate the transcription of Jun, a gene previously implicated in neuronal migration. Therefore in light of these studies and our data, in addition to LAF4 mutations associated with cortical atrophy and ID, there is increasing evidence that AFF proteins play important roles in neurodevelopment. AFF proteins were originally described as putative transcription factors based on the presence of a conserved transactivation domain ; however, only very few transcriptional targets have been confirmed to date. Our study suggests that Mdga2 gene is under the transcriptional control of Laf4.