Genetic control of postnatal human brain growth

Abstract

Purpose of review: Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here, we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms.

Recent findings: Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, post-mortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry.

Summary: To understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders.

Figure 1

Biological mechanisms underlying prenatal versus postnatal brain growth disorders. (Left panel) Prenatal brain growth disorders commonly arise from genetic causes associated with centrosomal abnormalities. Disruptions to centrosomal proteins may impact neuronal progenitor cell proliferation and differentiation, neuronal migration, and DNA repair responses (reviewed in [7]). (Right panel) Conversely, postnatal brain growth disorders mainly arise from genetic causes associated with disrupted connectivity (i.e., elaboration of axons and dendrites, spinogenesis and maturation, synaptogenesis and remodeling, and gliogenesis and myelination). Postnatal brain growth disorders may also result from childhood neurodegeneration.

Figure 2

Postnatal brain and head growth and underlying neurodevelopmental stages. The human brain and head size increase rapidly during the first and second postnatal years, followed by a more gradual increase into early adulthood. The increase in brain and head size largely results from elaboration of connectivity. Axon and dendrite growth and arborization continue after birth into early postnatal years. Synaptogenesis continues after birth, peaking at various points during childhood (depending on brain region). Synapses mature and remodel to form appropriate connections, and then undergo gradual pruning into early adulthood. Gliogenesis continues after birth, and glial cell differentiation and myelination continue into early adulthood.