Granule cells are continuously being generated in the dentate gyrus of the adult hippocampus. These adult-born neurons play an important role in memory formation and mood regulation, but the cellular mechanism underlying their polarized development, a process critical for their incorporation into functional circuits, remains unknown. Recently a study from the Institute of Neuroscience, Shanghai Institutes for Biological Sciences showed that the protein kinase LKB1 regulates polarized dendrite formation of adult hippocampal newborn neurons through asymmetric distribution of Golgi apparatus.

　　In the rodent central nervous system, LKB1 was reported to be an axon determinant for embryonic hippocampal and cortical pyramidal neurons. HUANG Wei and other colleagues in the laboratory of Dr. POO Mu-ming detected elevated LKB1 expression in immature neurons of adult hippocampus, which suggests that LKB1 may play a role in the development of adult-born granule cells.

　　To study the function of LKB1 during adult neurogenesis in vivo, they employed a retrovirus-mediated gene transfer approach to manipulate LKB1 expression. Surprisingly, they found that deletion of LKB1 or overexpression of dominant-negative LKB1 reduced the polarized initiation of the primary dendrite from the somata and disrupted its oriented growth toward the molecular layer.

　　They further demonstrated that this dendrite abnormality correlated with the dispersion of Golgi apparatus that normally accumulated at the base and within the initial segment of the primary dendrite, and was mimicked by disrupting Golgi organization via altering the expression of Golgi structural proteins GM130 or GRASP65.

　　These findings not only add a unique function to the growing list of LKB1 cellular actions, but also provide new clues to the subcellular mechanism of LKB1’s action.

　　This research entitled “Protein kinase LKB1 regulates polarized dendrite formation of adult hippocampal newborn neurons” was published online in PNAS on November 25, 2013. The work was supported by grants from the Ministry of Science and Technology (973 Program) and the Chinese Academy of Sciences (Strategic Priority Research Program).

　　(A) Elevated LKB1 expression in newborn neurons of adult dentate gyrus;

　　(B) A schematic diagram of retrovirus-mediated LKB1 gene deletion;

　　(C) and (D) LKB1 deletion in adult-born granule cells affects oriented initiation and extension of the primary dendrite;

　　(E) and (F) LKB1 deletion leads to dispersion of Golgi apparatus;

　　(G) Down-regulating LKB1 and manipulating of Golgi structural proteins lead to similar impairment of dendrite morphogenesis.