Type Ib BMP receptors mediate the rate of commissural axon extension through inhibition of cofilin activity

Yamauchi, Ken; Varadarajan, Supraja G.; Li, Joseph E.; Butler, Samantha J.

doi:10.1242/dev.089524

Cited by 24 publications

(28 citation statements)

References 41 publications

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“…Taken together with our recent studies (Hazen et al, 2011; Yamauchi et al, 2008; Yamauchi et al, 2012), we have determined that these activities are differentially translated at both the receptor and second messenger level in dorsal spinal neurons. Thus, a shared activity of the type I Bmprs mediates the specification of the dorsal-most cell fates primarily through the Smad5 intermediate.…”

Section: Discussionsupporting

confidence: 65%

“…Thus, a shared activity of the type I Bmprs mediates the specification of the dorsal-most cell fates primarily through the Smad5 intermediate. In contrast, the activation of BmprIb alone regulates rate of growth of commissural axons, by activating Limk1 (Yamauchi, 2011) and (putatively) Smad1. Future studies will resolve whether Smad1 has a novel activity orchestrating cytoskeletal dynamics with Limk1 or whether the role of Smad1 reflects a requirement for transcriptional regulation during the formation of neural circuits.…”

Section: Discussionmentioning

confidence: 99%

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BMP receptor-activated Smads confer diverse functions during the development of the dorsal spinal cord

Hazen

Andrews

Umans

et al. 2012

Developmental Biology

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Bone Morphogenetic Proteins (BMPs) have multiple activities in the developing spinal cord: they specify the identity of the dorsal-most neuronal populations and then direct the trajectories of dorsal interneuron (dI) 1 commissural axons. How are these activities decoded by dorsal neurons to result in different cellular outcomes? Our previous studies have shown that the diverse functions of the BMPs are mediated by the canonical family of BMP receptors and then regulated by specific inhibitory (I) Smads, which block the activity of a complex of Smad second messengers. However, the extent to which this complex translates the different activities of the BMPs in the spinal cord has remained unresolved. Here, we demonstrate that the receptor-activated (R) Smads, Smad1 and Smad5 play distinct roles mediating the abilities of the BMPs to direct cell fate specification and axon outgrowth. Smad1 and Smad5 occupy spatially distinct compartments within the spinal cord, with Smad5 primarily associated with neural progenitors and Smad1 with differentiated neurons. Consistent with this expression profile, loss of function experiments in mouse embryos reveal that Smad5 is required for the acquisition of dorsal spinal neuron identities whereas Smad1 is critical for the regulation of dI1 axon outgrowth. Thus the R-Smads, like the I-Smads, have discrete roles mediating BMP-dependent cellular processes during spinal interneuron development.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

BMP receptor-activated Smads confer diverse functions during the development of the dorsal spinal cord

Hazen

Andrews

Umans

et al. 2012

Developmental Biology

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“…Our studies [3], [42], and those of others [43], [44], [45], [46], [47], [48] have shown that guidance factors can regulate the rate of axon extension by controlling the activity of cofilin and its negative regulator Limk1. Cofilin acts to depolymerize or sever actin [4].…”

Section: Discussionsupporting

confidence: 56%

Bilaterally Symmetric Populations of Chicken dI1 (Commissural) Axons Cross the Floor Plate Independently of Each Other

Phan

Butler

2013

PLoS ONE

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Axons use temporal and directional guidance cues at intermediate targets to set the rate and direction of growth towards their synaptic targets. Our recent studies have shown that disrupting the temporal guidance process, by unilaterally accelerating the rate at which spinal dI1 (commissural) axons grow, resulted in turning errors both in the ventral spinal cord and after crossing the floor plate. Here we investigate a mechanistic explanation for these defects: the accelerated dI1 axons arrive in the ventral spinal cord before necessary fasciculation cues from incoming dI1 axons from the opposite side of the spinal cord. The identification of such an interaction would support a model of selective fasciculation whereby the pioneering dI1 axons serve as guides for the processes of the bilaterally symmetrical population of dI1 neurons. To test this model, we first developed the ability to “double” in ovo electroporate the embryonic chicken spinal cord to independently manipulate the rate of growth of the two bilateral populations of dI1 axons. Second, we examined the requirement for a putative bilateral interaction by unilaterally ablating the dI1 population in cultured explants of chicken embryonic spinal cord. Surprisingly, we find no evidence for a bilateral dI1 axon interaction, rather dI1 axons appear to project independently of each other.

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“…Most of the data arise from studies of the sensory projection neurons of the spinal cord. BMP-7 and GDF-7 supplied by the roof plate orient axons of commissural neurons away from the roof plate and regulate their rate of extension through the spinal cord toward the floor plate (Augsburger et al, 1999; Butler and Dodd, 2003; Yamauchi et al, 2008, 2013; Sanchez-Camacho and Bovolenta, 2009). Guideposts are discrete groups of glial or neuronal cells that provide discontinuous information in intermediate positions along the path of growing axons (Sanchez-Camacho and Bovolenta, 2009).…”

Section: Bmps In Nervous System Development and Maintenancementioning

confidence: 99%

BMP signaling in telencephalic neural cell specification and maturation

Gámez¹,

Rodríguez-Carballo²,

Ventura³

2013

Front. Cell. Neurosci.

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Bone morphogenetic proteins (BMPs) make up a family of morphogens that are critical for patterning, development, and function of the central and peripheral nervous system. Their effects on neural cells are pleiotropic and highly dynamic depending on the stage of development and the local niche. Neural cells display a broad expression profile of BMP ligands, receptors, and transducer molecules. Moreover, interactions of BMP signaling with other incoming morphogens and signaling pathways are crucial for most of these processes. The key role of BMP signaling suggests that it includes many regulatory mechanisms that restrict BMP activity both temporally and spatially. BMPs affect neural cell fate specification in a dynamic fashion. Initially they inhibit proliferation of neural precursors and promote the first steps in neuronal differentiation. Later on, BMP signaling effects switch from neuronal induction to promotion of astroglial identity and inhibition of neuronal or oligodendroglial lineage commitment. Furthermore, in postmitotic cells, BMPs regulate cell survival and death, to modulate neuronal subtype specification, promote dendritic and axonal growth and induce synapse formation and stabilization. In this review, we examine the canonical and non-canonical mechanisms of BMP signal transduction. Moreover, we focus on the specific role of BMPs in the nervous system including their ability to regulate neural stem cell proliferation, self-renewal, lineage specification, and neuronal function.

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Type Ib BMP receptors mediate the rate of commissural axon extension through inhibition of cofilin activity

Cited by 24 publications

References 41 publications

BMP receptor-activated Smads confer diverse functions during the development of the dorsal spinal cord

BMP receptor-activated Smads confer diverse functions during the development of the dorsal spinal cord

Bilaterally Symmetric Populations of Chicken dI1 (Commissural) Axons Cross the Floor Plate Independently of Each Other

BMP signaling in telencephalic neural cell specification and maturation

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