EphA7 signaling guides cortical dendritic development and spine maturation.
The process by which excitatory neurons are generated and mature during the development of the cerebral cortex occurs in a stereotyped manner; coordinated neuronal birth, migration, and differentiation during embryonic and early postnatal life are prerequisites for selective synaptic connections that mediate meaningful neurotransmission in maturity. Normal cortical function depends upon the proper elaboration of neurons, including the initial extension of cellular processes that lead to the formation of axons and dendrites and the subsequent maturation of synapses. Here, we examine the role of cell-based signaling via the receptor tyrosine kinase EphA7 in guiding the extension and maturation of cortical dendrites. EphA7, localized to dendritic shafts and spines of pyramidal cells, is uniquely expressed during cortical neuronal development. On patterned substrates, EphA7 signaling restricts dendritic extent, with Src and Tsc1 serving as downstream mediators. Perturbation of EphA7 signaling in vitro and in vivo alters dendritic elaboration: Dendrites are longer and more complex when EphA7 is absent and are shorter and simpler when EphA7 is ectopically expressed. Later in neuronal maturation, EphA7 influences protrusions from dendritic shafts and the assembling of synaptic components. Indeed, synaptic function relies on EphA7; the electrophysiological maturation of pyramidal neurons is delayed in cultures lacking EphA7, indicating that EphA7 enhances synaptic function. These results provide evidence of roles for Eph signaling, first in limiting the elaboration of cortical neuronal dendrites and then in coordinating the maturation and function of synapses.
Departments of Biology and Pharmacology and Physiology, Interdisciplinary Program in Neuroscience, and Graduate Program in Physiology and Biophysics, Georgetown University, Washington, DC 20057.
Meredith A
MA
Clifford
Wardah
W
Athar
Carrie E
CE
Leonard
Alexandra
A
Russo
Paul J
PJ
Sampognaro
Marie-Sophie
MS
Van der Goes
Denver A
DA
Burton
Xiumei
X
Zhao
Rupa R
RR
Lalchandani
Mustafa
M
Sahin
Stefano
S
Vicini
Maria J
MJ
Donoghue
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism*; D036386:Ephrin-A5 / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D008024:Ligands; D051379:Mice; D055495:Neurogenesis; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D036141:Receptor, EphA7 / Q000378:metabolism*; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D036386:Ephrin-A5; D008024:Ligands; C000624651:Tsc1 protein, mouse; C000624652:Tsc1 protein, rat; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D036141:Receptor, EphA7; C581330:epha7 receptor, mouse; D019061:src-Family Kinases
dendritic spine; neurogenesis; synaptogenesis