Subsequently, the process of neuronal morphogenesis involves
the formation of cellular polarization that leads to the development of axonal growth cones which begin traversing the brain, forming its complex circuitry. This period of development is marked by profound axon and dendrite branching and arborization that eventually determines the axons and dendrites of any given neuron.5,6 Figure 1. Timeline of human brain development. This figure represents Inhibitors,research,lifescience,medical a schematized conceptualization of the steps during human brain development. Time in weeks post-conception and then postnatal years are shown along the horizontal axis. Birth and puberty and … These aforementioned neurodevelopmental events are typically considered experience-independent processes. In other words, intrinsic genetic factors regulate each mechanism independent of sensory experience of the external world. Interestingly, Inhibitors,research,lifescience,medical there are many monogenic diseases that appear to affect one or various given stages above. For example, disorders that cause small brain size at birth, called primary microcephaly, result from a large number of single gene mutations that appear to affect neurogenesis.7 Similarly, other monogenic disorders may result in abnormal patterning such as sonic hedgehog mutations or other mutations that may
cause Inhibitors,research,lifescience,medical holoprosencephaly (failure of the forebrain to develop into two hemispheres).8 Finally, there are a number of disorders of cortical migration that lead to abnormal layering of the brain
or abnormal Inhibitors,research,lifescience,medical gyrus and sulcus formation.9 Although there are exceptions, the above disorders have not been typically associated with autism symptoms; however, instead highly related conditions such as intellectual disability and epilepsy are more frequently described, along with the associated structural brain malformation. Interestingly, with respect to axon outgrowth, there are a number of monogenic disorders that may involve Selleck GS-1101 abnormalities of axon growth and/or targeting that have been associated with autistic symptoms. Joubert syndrome, Inhibitors,research,lifescience,medical for example, is a genetically heterogeneous condition that displays abnormalities in axon outgrowth and has been associated with autism symptoms.10 Similarly, one neurodevelopmental abnormality in tuberous sclerosis (TSC) is also abnormal axon growth, and TSC is also recurrently although inconsistently associated with autism.11 Joubert Parvulin syndrome is generally associated with structural brain malformations. TSC is most frequently associated with a variety of morphologic abnormalities including tubers, but also with abnormalities of the corpus callosum. Growth of the corpus callosum has frequently been cited as an indicator of problems in the axon growth step of neurodevelopment. Indeed, isolated agenesis, hypogenesis, or dysgenesis of the corpus callosum have been associated with an increase in autism symptoms.