Molecular mechanisms for morphogenesis of the central nervous system in mammals

The mammalian central nervous system (CNS) is a highly organized structure. In the beginning of CNS development, neural precursor/stem cells are dividing in the neuroepithelium. After a while, these precursors gradually start to differentiate into neurons and glial cells. Various factors are involved in the proliferation and differentiation of neural precursors. Recent studies have demonstrated that the basic helix-loop-helix (bHLH) transcription factors play important roles in differentiation processes. Hairy and Enhancer of split homolog (HES) 1 and HES5 are bHLH-type repressors and inhibit neural differentiation. Mammalian achaete-scute complex homolog (MASH) 1 and mammalian atonal homolog (MATH) 1 are positive bHLH regulators expressed in neural precursors. A balance between positive and negative regulators may determine whether differentiation proceeds or not. The data suggest that this balance is controlled by Notch signaling. Other extracellular signals also govern CNS morphogenesis. To elaborate the primary shape of the CNS, proliferation of neural precursors should be strictly regulated in a spatial and temporal manner. A recent study suggests that a Sonic hedgehog-dependent signaling relay controls growth of the diencephalon and midbrain. Nutrition is another critical factor for development. Expression analysis folate binding protein 1 implied the close association between folate uptake and anterior neural tube closure.