Role of IGF Signaling in Olfactory Sensory Map Formation and Axon Guidance

Scolnick, Jonathan; Cui, Kai; Duggan, Cynthia; Xuan, Shouhong; Yuan, Xiao-bing; Efstratiadis, Argiris; Ngai, John

doi:10.1016/j.neuron.2008.01.027

Cited by 78 publications

(78 citation statements)

References 59 publications

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“…However, more recent findings have linked IGF signaling with pleiotropic effects including cellular differentiation, axon outgrowth and polarity, cell migration and patterning, and cell survival (Fukudome et al, 2003;VicarioAbejó n et al, 2003;Ye and D'Ercole, 2006;Scolnick et al, 2008). The results presented here are consistent with a broader role for IGF signaling as many of the changes observed in the inner ears of Igf1r Ϫ/Ϫ mutants are not consistent with a decrease in proliferation.…”

Section: Igf Signaling During Initial Cochlear Developmentsupporting

confidence: 61%

“…During embryonic development, IGF signaling plays an important role in determining body size by promoting cell proliferation and survival . In the nervous system, IGF signaling has been shown to regulate differentiation of oligodendrocytes and to promote growth cone formation and axon out-growth (Hsieh et al, 2004;Laurino et al, 2005;Scolnick et al, 2008). However, a specific role(s) for IGF signaling in inner ear development has not been fully examined.…”

Section: Introductionmentioning

confidence: 99%

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Insulin-Like Growth Factor Signaling Regulates the Timing of Sensory Cell Differentiation in the Mouse Cochlea

Okano¹,

Xuan²,

Kelley³

2011

J. Neurosci.

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The mammalian auditory sensory epithelium, the organ of Corti, is a highly ordered cellular structure that comprises two types of auditory hair cells and several types of nonsensory supporting cells. During embryogenesis, a stereotyped sequence of cellular and molecular events is required for its development. These processes are assumed to be regulated by multiple growth and transcription factors. However, the majority of these factors have not been identified. One potential regulator of cochlear development is the insulinlike growth factor (IGF) signaling family. To examine the roles of the IGF pathway in inner ear formation, cochleae from Igf1r mutant mice were analyzed. Deletion of Igf1r leads to several changes in inner ear development including a shortened cochlear duct, a decrease in the total number of cochlear hair cells, and defects in the formation of the semicircular canals. In addition, maturation of the cochlear sensory epithelium was delayed at the transition point between cellular proliferation and differentiation. To determine the molecular basis for these defects, inhibition of IGF signaling was replicated pharmacologically in vitro. Results indicated that IGF signaling regulates cochlear length and hair cell number as well as Atoh1 expression through the phosphatidylinositol 3-kinase/Akt signaling pathway. These results demonstrate novel roles for IGF signaling in inner ear development including regulation of vestibular formation, length of the cochlear duct, and the number of cochlear hair cells. The results also provide new insights regarding the pathological processes that underlie auditory defects in the absence of IGF signaling in both humans and mice.

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Section: Igf Signaling During Initial Cochlear Developmentsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor Signaling Regulates the Timing of Sensory Cell Differentiation in the Mouse Cochlea

Okano¹,

Xuan²,

Kelley³

2011

J. Neurosci.

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“…Igf2 belongs to a family of secreted growth factors including insulin-like growth factor 1 and 2, both able to activate receptor tyrosine kinases that are expressed in the CNS (Hetts et al, 1997;Scolnick et al, 2008). In contrast to Igf1, which plays a role in axonal growth and pathfinding, neuronal progenitor proliferation, and synaptic homeostasis, little is known about the physiological function of Igf2 in the nervous system (Chiu et al, 2008;Chiu and Cline, 2010).…”

Section: Discussionmentioning

confidence: 99%

IκB Kinase/Nuclear Factor κB-Dependent Insulin-Like Growth Factor 2 (Igf2) Expression Regulates Synapse Formation and Spine Maturation via Igf2 Receptor Signaling

Schmeißer

Baumann²,

Johannsen³

et al. 2012

J. Neurosci.

117

107

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“…Other trophic factors have been proposed to play important guidance roles. Insulin-like growth factor (IGF) has been proposed to act as a chemoattractant for olfactory axons (Scolnick et al 2008). Hepatocyte growth factor (HGF) promotes the survival of motor neurons, is expressed in branchial arches, is required for normal extension of the hypoglossal nerve, and attracts cranial motor axons in vitro (Ebens et.…”

Section: Trophic Signalsmentioning

confidence: 99%

Cellular Strategies of Axonal Pathfinding

Raper

Mason

2010

Cold Spring Harbor Perspectives in Biology

157

130

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Axons follow highly stereotyped and reproducible trajectories to their targets. In this review we address the properties of the first pioneer neurons to grow in the developing nervous system and what has been learned over the past several decades about the extracellular and cell surface substrata on which axons grow. We then discuss the types of guidance cues and their receptors that influence axon extension, what determines where cues are expressed, and how axons respond to the cues they encounter in their environment.T his article provides an overview of how growth cones respond to the cellular substrata and molecular cues they encounter as they extend through the developing nervous system. It elaborates on the primer by Kolodkin and TessierLavigne (2010) and touches on many of the topics covered in greater detail in the articles that follow. The first sections describe how axons extend in a directed manner, the substrata on which they grow, interactions between pioneer and follower axons, and growth cone behaviors in emerging tracts and at decision points. The subsequent sections discuss examples of specific cues, their distributions, how their distributions are determined, and how growth cones integrate multiple cues during pathfinding. AXONS EXTEND IN VIVO IN A DIRECTED MANNERThe first person to visualize the growing tips of axons, Ramon y Cajal, recognized that axons for the most part grow very efficiently towards their ultimate targets. He was a strong advocate for axons finding their way in response to chemotactic cues:"If one admits that neuroblasts are endowed with chemotactic properties, then one might also imagine that they are capable of ameboid movements, initiated by factors secreted from epithelial, neural, or mesodermal elements. As a result, their processes may be oriented in the direction of chemical gradients, and thus guided to the secreting cells" (Ramon y Cajal 1892; trans. English, 1995).This surprisingly modern outlook emphasizing directed guidance was temporarily derailed by the views of Weiss during the 1920s and 1930s. He first argued that functional specificity did not arise as a consequence of specific axonal connections (Weiss 1936), and later argued that nonspecific mechanical guidance cues play a predominant role in guiding axons and organizing them into nerves and tracts

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Role of IGF Signaling in Olfactory Sensory Map Formation and Axon Guidance

Cited by 78 publications

References 59 publications

Insulin-Like Growth Factor Signaling Regulates the Timing of Sensory Cell Differentiation in the Mouse Cochlea

Insulin-Like Growth Factor Signaling Regulates the Timing of Sensory Cell Differentiation in the Mouse Cochlea

IκB Kinase/Nuclear Factor κB-Dependent Insulin-Like Growth Factor 2 (Igf2) Expression Regulates Synapse Formation and Spine Maturation via Igf2 Receptor Signaling

Cellular Strategies of Axonal Pathfinding

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