The Research On Development Of Corpus Callosum In DCC^kanga Mouse

DCC（Deleted in Colorectal Cancer） is a receptor of Netrin-1，it mainlyincludes the extracellular domain which combines with its ligand, transmembranedomain which rich in hydrophobic amino acids，intracellular domain which consist ofP1，P2and P3. DCC serves as a receptor protein for the guidance signaling cueNetrin-1to regulate axon attraction and the formation of dorsal telencephaliccommissures. Studies have shown that both the corpus callosum and the anteriorcommissure were missing in DCC^kangamice，while the impact of DCC P3-domain onmigration of neuron and development of cerebral cortex is still unknown. Thelaminated structure in mammalian cerebral cortex develops in a stereotypicalbirth-date-dependent “inside-out” pattern, which is established by differentiation ofneural progenitor cells and neuron migration with sequential changes of migratorymode. Coordinated migration of cortical neurons in the developing and adult cerebralcortex is especially essential for its proper function, and migration defects can causeneurological and psychiatric diseases. Such as schizophrenosis, epilepsia, AD, PD andso on.Here，we have researched the role of DCC protein in the formation of corpuscallosum. As expected，We have confirmed the loss of corpus callosum in DCC^kangamice in P7by nissil staining and DiI trace. We have found that DCC is mainlyexpressed in the mouse brain at embryonic stages，and the expression pattern in theintermediate zone of cerebral cortex at largely. The brain of DCC+/-and DCC^kangamiceare more small campared with WT，Consistent with this finding，Map2expressionwere decreased in the CP，and CS56expression were increased in the SP in theDCC+/-and DCC^kangamice neonatal cortex. In DCC+/-and DCC^kangamice layers II^IVwere thinner，whereas layers V^VI were more thicker at P7. BrdU birth datingrevealed that late-generated neurons labeled by BrdU injections administered at E14.5or E16.5, and destined to cortical layers II^IV, were disorganized and more located inoutside of cerebral cortex. In addition，we detected loss of DCC P3-domain in DCC^kangaresults in callosal dysgenesis. Commissural axon guidance is thought todepend upon the integrity of midline cells in the glial wedge, indusium griseum,midline zipper and glial sling. To examine the formation of these glial structures inDCC mutant neonates, we performed immunohistochemistry for GFAP in knockoutand control littermates at postnatal day P0. The glial wedge, indusium griseum andmidline zipper astroglia were clearly visible at this age in control mice, as previouslydescribed. In contrast, indusium griseum astroglia were absent in the DCC+/-andDCC^kangamice. Finally, we found that DCC+/-and DCC^kangamice had defectivemigration of cells from the glial wedge to the indusium griseum. Together, our resultsindicate that neuronal migration in the developing cortex and the formation of corpuscallosum requires the DCC P3-domain.