Chalisa Prarasri

Numb (N) and its closely related homolog, Numblike (NL) are
adaptor proteins shown to play a role in regulating cell functions
involved in neural development. My studies have indicated that N/
NL are expressed by all motor neurons (MNs) in the embryonic mouse
spinal cord (SC). Conditional double knockout (cKO) mice with N/
NL missing in MNs display irregular ventral SC morphology and
aberrant MN nucleic migration through the ventral horn. To
determine how N/NL interact… Show more

Numb (N) and its closely related homolog, Numblike (NL) are
adaptor proteins shown to play a role in regulating cell functions
involved in neural development. My studies have indicated that N/
NL are expressed by all motor neurons (MNs) in the embryonic mouse
spinal cord (SC). Conditional double knockout (cKO) mice with N/
NL missing in MNs display irregular ventral SC morphology and
aberrant MN nucleic migration through the ventral horn. To
determine how N/NL interact with cell machinery to keep MN soma
in place within the SC, we investigated four possible causes of this
aberrant MN nucleic migration: 1) the mutant SC morphology causes
the basal lamina to be disrupted 2) the mutant SC morphology causes
boundary cap cells (BCCs), which keep MN nuclei in the SC, to be
mispositioned 3) loss of N/NL in MNs disrupts the signaling between
BCCs and MNs 4) N/NL directly prevent nucleokinesis by interacting
with components of the cytoskeletal machinery. Immunohistochemical
and in situ hybridization analyses suggest that the aberrant nucleic
migration observed in N/NL cKO MNs cannot be accounted for by a
disruption of the basal lamina or disruption of the signaling between
MNs and BCCs. Therefore, we are currently investigating whether
N/NL directly interact with nucleokinesis components and block
movement of MN nuclei. This research is significant because MNs
require sensory innervation from the brain and other neurons in the
SC in order to function properly, making the location of the cell body
critical. Show less

Growth factor signaling pathways are commonly transduced through receptor tyrosine kinases (RTKs) and are responsible for controlling a broad spectrum of developmental processes, including proliferation, differentiation, migration, and survival. In vertebrates, Sprouty 1, 2, 3, and 4 constitute a family of intracellular inhibitors of RTK signaling. Knockout of each of the Sprouty proteins has been shown to result in phenotypes associated with excess growth factor signaling -- most notably… Show more

Growth factor signaling pathways are commonly transduced through receptor tyrosine kinases (RTKs) and are responsible for controlling a broad spectrum of developmental processes, including proliferation, differentiation, migration, and survival. In vertebrates, Sprouty 1, 2, 3, and 4 constitute a family of intracellular inhibitors of RTK signaling. Knockout of each of the Sprouty proteins has been shown to result in phenotypes associated with excess growth factor signaling -- most notably, increased axonal branching in a variety of tissues. Few studies, however, have investigated the role of Sprouty proteins in motor neurons. In this study, I have characterized Sprouty gene expression in embryonic wild-type mouse and chick spinal cords by in situ hybridization during the period of motor neuron differentiation. I have further characterized Sprouty-expressing motor neurons by determining the coexpression of Sprouty with known markers of motor neuron columns. In order to understand the role of Sprouty proteins in motor neuron development, substantial progress has been made toward creating a misexpression construct designed to overexpress the relevant Sprouty genes specifically in motor neurons. This construct will be electroporated in ovo into the developing chick spinal cord to determine the relevant Sprouty overexpression phenotypes. This study will further the understanding of the role of Sprouty proteins in the intracellular interpretation of environmental signals in motor neurons. Show less