Fat family atypical cadherins are known to regulate planar cell polarity and growth control in Drosophila. In mammals, four Fat genes (Fat1 to Fat4) have been identified but relatively little is known about how these regulate mammalian embryogenesis. Here, Helen McNeill and co-workers identify a role for Fat proteins in regulating various aspects of brain development in mice (p. ). Using mutant mice, the researchers first identify a role for Fat1 in neural tube closure; Fat1 mutants display cranial neural tube closure defects leading to exencephaly. They further show that the cortex of these mutant embryos exhibits elongated ventricles, linked to an increase in radial precursor cell proliferation. Accordingly, the knockdown of Fat1 by in utero electroporation in the developing cortex causes an increase in radial precursor cell proliferation and perturbs neuronal differentiation and migration. The researchers further show that Fat4 interacts genetically with Fat1 to control these processes. Finally, they reveal that Fat1 and Fat4 bind to distinct sets of actin regulators and apical junction proteins, respectively. Together, these findings lead the authors to propose a model in which Fat1-Fat4 dimer formation brings together diverse proteins at apical junctions to regulate both apical constriction and progenitor cell divisions in the neural tube.
