Graduate Program: Ph.D.
Formation of axon and dendrite begins when neurons complete migration and reach their
final destination in different parts of the brain. Ras GTPases are known to regulate
cytoskeletal changes that lead to axon and dendrite formation in the developing brain.
Dab2IP, DOC-2/DAB2 interacting protein, is one of the RasGAP proteins that can bind to active
Ras and result in terminating the signal event. The gene of Dab2IPappears to undergo
alternative splicing to make different isoforms. In human, at least three different
Dab2IP splice variants have been reported to GenBank database, though there are two
Dab2IP isoforms reported in mouse and just one in rat brain. These isoforms have some
varieties at the C-terminus and N-terminus that probably differ their biological functions.
The team that I’m working with have found the expression of each isoform in mouse
developing brain is tissue and time specific. In order to investigate the physiological
role of different isoforms, we generated a Dab2IP knock-down mouse line with a retroviral
gene-trap insertion. Following gene trapping we observed a delay in the development
of Purkinje cell dendrites in the cerebellum of knock down mice compared to wild type.
As this observation confirms the important role of this protein in the brain development,
I’m interested to discover all different isoforms and determine their biological functions
in neurons through their subcellular localization and the mechanism that they are
involved in mouse brain over time.