Expression profiling and function elucidation of anaplastic lymphoma kinase in the developing nervous system
Hurley, Shawn Patrick.
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During embryonic development, complex events such as cellular proliferation, differentiation, survival, and guidance of axons are orchestrated and regulated by a variety of extracellular signals. Receptor tyrosine kinases mediate many of these events with several playing critical roles in neuronal survival and axonal guidance. It is evident that not all the receptor tyrosine kinases that play key roles in regulating neuronal development have been identified. In these studies, we have characterized the spatial-temporal expression profile of a recently identified receptor tyrosine kinase, anaplastic lymphoma kinase (ALK), in embryonic chick by means of whole mount in situ hybridization in conjunction with immunohistochemistry. Our findings reveal that Alk is expressed in sympathetic and dorsal root ganglia as early as stage 19.In addition, mRNA is expressed from stage 23/24 (E4) until stage 39 (E13) in discrete motor neuron subsets of chick spinal cord along with a select group of muscles that are innervated by one of these particular motor neuron clusters. Based on these findings, we conducted loss-of-function analyses by means of in ovo RNA interference (RNAi) to determine the role of ALK as it pertains to development of the spinal cord. Results indicate that ALK is involved in the survival of spinal neurons including motor neurons and possibly interneurons. Hence, the data presented here identify ALK as a novel receptor for regulating critical events in the development of the central nervous system and, potentially, the peripheral nervous system.