research @ THE TAN LAB

The hippocampus is a brain region important for learning and memory, spatial navigation, and mood regulation. Structural and functional changes of the hippocampus have been found in several neurological disorders, such as epilepsy and Alzheimer's disease. Using the hippocampus as a model system, we study how diverse cells types are produced, maintained or eliminated, and integrated into the brain circuit. Knowledge gained from our study may shed light on the pathogenic mechanism of neurological diseases and may facilitate the development of more effective treatments.

In contrast to many other cortical regions, which complete neurogenesis by birth, the dentate gyrus of the hippocampus undergoes protracted postnatal development.

How is early postnatal neurogenesis regulated?

What controls the migration of progenitors and newborn neurons?

What factors promote precise projection of newly generated neurons?

Most neurons in our brains arise during embryonic development and around birth. However, the mammalian brain retains the capacity to generate new neurons even throughout adulthood. 

The dentate gyrus of the hippocampus is a brain region where new neurons are continuously produced. The adult-born neurons from this region are thought to be important for learning, memory formation and mood regulation.

We are particularly interested in neuronal maturation during adult hippocampal neurogenesis, specifically, the stages of neuroblast and immature neuron maturation.

These are some of the questions that we are studying:

What regulates the initiation and termination of neuronal migration?

How is the dendritic architecture of new-born granule neurons built?

What confers vulnerability to cell death?

In the developing brain, the birth of neurons is followed by the death of 20‒40% of these neurons, raising the question of the importance of such demise for the adult brain. Cajal-Retzius cells – pioneer neurons of the embryonic brain but then almost completely disappear – present a unique system to address this question. Incomplete CR cell removal has been described in human brain pathologies including epilepsy, opening the intriguing possibility that CR cell death plays a constructive role in sculpting the mature cerebral cortex. 

Our research questions are:

What regulates the developmental cell death of Cajal-Retzius cells?

What are the roles of Cajal-Retzius cells in the adult hippocampus?

How may Cajal-Retzius cells play a role in epilepsy?