How is the pace of neurogenesis controlled?
Jun Hatakeyama, Ph.D.

How are the correct size and shape of the brain established during development? How is the regionally distinct cellular organization of the brain constructed? One of the key issues here is the balance of proliferation/self-renewal and differentiation of the neural progenitors. In fact, this balance appears to be different spatially and temporally. Notch signaling plays a pivotal role in regulating this balance, yet how this signaling system is practically involved in the spatially and temporally distinct balance remains poorly understood.
We found that newly born neurons unexpectedly retain their contacts with the progenitors through the apical endfeet located at the ventricular lumen for a certain period of time. Our results indicated that those transiently retained neuronal endfeet play an important role in the kinetic regulation of neurogenesis by which the pace of neuron production is likely controlled. For a molecular mechanism underlying it, we provide evidence that Notch signaling is facilitated by the contact of the apical endfeet, which is regulated by the dynamics of adherens junction. Thus, the functions of adherens junction are not only for maintaining the architecture of the neural tube but also for the stem cell niche of the neural progenitors.

An extrinsic mechanism regulating cortical development in the mouse brain
Haruka Takemoto-Sato, Ph.D.

The cerebral cortex is the largest component of the mammalian brain involved in functions such as sensory perception and learning. It is subdivided into a number of functional areas based on the histological features. However, developmental mechanisms that regulate area formation are largely unknown. Since the projection pattern of the thalamic afferent correlates with histological features among areas, we hypothesized that thalamic afferent plays an important role in specialization of areas by releasing extrinsic factor(s) that promote the survival and/or differentiation of cortical neurons. Here, we investigated the role of thalamic afferent in the cortical area formation in vivo. Elimination of the thalamic afferent led to a reduction in neuronal number in the target cortical area. As candidates for the afferent-derived secretory protein that regulates cortical development, we have found that NRN1 and VGF are expressed at the right time and place with appropriate functions. These results provide evidence for the extrinsic mechanism of cortical development in which thalamic afferent regulates survival of cortical neurons possibly via NRN1 and VGF secreted from the thalamic afferent.