This suggests that Laf4 has a stimulatory role on gene transcription, consistent with data obtained from the Af4-containing complex. This is also in accordance with a previous study showing that LAF4, like AF4 and AF5Q31, interacts with AF9/ENL protein, positive transcription elongation factor b and histone-H3 methyltransferase DOT1L. In further support of Laf4 function as a transcription regulator, overexpression of Laf4 in cortical cells led to an increase in BTAF1 RNA polymerase II, part of the pre-initiation transcription factor II D complex, and Max gene associated which binds to the transcription factor Max, a facultative component of the MLL1 complex. This suggests that Laf4 likely acts in collaboration with other transcription factors or chromatin remodellers to control gene transcription. Here, we demonstrate for the first time that Mdga2 is involved in cell migration during the process of cortical layering; indeed Mdga2 Fulvestrant over-expression was able to rescue the migration deficit resulting from Laf4 knockdown. It is noteworthy that while Mdga2 over-expression largely rescued the deficit, there was not a complete rescue. Interestingly, Mdga1, Mdga2 closest homologue, is required for neuronal migration. Thus, while Mdga2 plays a major role in Laf4-regulated migration, it may not be the only effector gene. Recent studies have shown that reduced levels of Mdga2 in open-book preparations from chicken embryos affect rostral growth of commissural axons. Moreover, Mdga2, like Mdga1, binds to neuroligin-2, and binding of Mdga1 to neuroligin2 inhibits neuroligin-2 synapse-promoting activity leading to reduction of synapse development and synaptic transmission in culture ; importantly, neuroligin-2 is expressed in the mouse brain from E18 to P25. Together, these studies suggest that, in addition to its role in cellular migration, Mdga2 may also affect axon growth and synapse formation in the developing cortex. Our current study has shed some important new light on the potential mechanisms underlying the developmental delay and cortical atrophy observed from a heterozygous LAF4 deletion in humans and repeat expansion silencing of the gene associated with ID. The cell migration data presented here may represent a greater degree of LAF4 knockdown than observed in these human conditions; but importantly, testing of additional shRNAs demonstrated that knockdown of Laf4 to levels that might be expected by haploinsufficiency results in alterations in expression of a transcriptional target of Laf4. Consequently, our results suggest that loss of LAF4 expression may have resulted in defective cell migration during early cortical development. Mutations in genes involved in neuronal cell migration have previously been associated with developmental delay and ID in humans. For example, doublecortin is associated with band heterotopia, a condition with severe intellectual disability and epilepsy, and which has been shown to be a consequence of radial migration deficits during neocortex development. Doublecortin is also associated with lissencephaly, a disease presenting severe ID, seizures and brain with reduced gyration. Similarly, mutations in LIS1, a gene involved in radial cortical neuronal migration, have also been associated with lissencephaly.