Target-derived BMP signaling limits sensory neuron number and the extent of peripheral innervation in vivo

Guha, Udayan; Gomes, William A.; Samanta, Jayshree; Gupta, Meenakshi; Rice, Frank L.; Kessler, John A.

doi:10.1242/dev.01013

Cited by 69 publications

(55 citation statements)

References 66 publications

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“…To determine the physiological significance of the in vitro observations, the effects of inhibiting BMP function in the gut were examined in animals that overexpress the BMP antagonist noggin under the control of the NSE promoter (Guha et al, 2004). The NSE promoter was selected to direct noggin overexpression in the gut to the developing ENS and to delay its occurrence until neurons begin to differentiate.…”

Section: Discussionmentioning

confidence: 99%

“…The promoter for neuron-specific enolase (NSE) was used to direct noggin overexpression in the NSE-noggin mice to neurons (Forss-Petter et al, 1990) and enteroendocrine cells, both of which normally express NSE in the bowel (Schmechel et al, 1980;Bishop et al, 1985;Tam and Lister, 1986;Scheuermann et al, 1989;Hearn et al, 1999). The coding sequence of noggin was followed by those encoding an internal ribosome entry site (IRES) and enhanced green fluorescent protein (EGFP) as part of a bicistronic transcript, so that the single NSE promoter would direct expression of the EGFP reporter as well as noggin to facilitate detection of transgene expression (Chalazonitis et al, 2003a,b;Guha, 2003;Guha et al, 2004). The postnatal small intestine was examined in 11 heterozygous and four homozygous NSE-noggin mice, as well as in seven of their wild-type littermates [ages postnatal day 26 (P26) to P34].…”

Section: Methodsmentioning

confidence: 99%

“…To determine whether BMP-2 and BMP-4 physiologically regulate development of enteric neurons and their expression of TrkC, we quantified the total number of neurons and that of the TrkC-expressing subset in the intestines of transgenic mice that overexpress the BMP antagonist noggin (Guha et al, 2004). Noggin overexpression was directed to neurons by using the NSE promoter to drive expression of a bicistronic noggin-IRES-EGFP transgene.…”

Section: Enteric Neuronal Hyperplasia Occurs In Mice That Overexpressmentioning

confidence: 99%

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Bone Morphogenetic Protein-2 and -4 Limit the Number of Enteric Neurons But Promote Development of a TrkC-Expressing Neurotrophin-3-Dependent Subset

Chalazonitis¹,

D’Autréaux²,

Guha³

et al. 2004

J. Neurosci.

121

212

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The hypothesis that BMPs (bone morphogenetic proteins), which act early in gut morphogenesis, also regulate specification and differentiation in the developing enteric nervous system (ENS) was tested. Expression of BMP-2 and BMP-4, BMPR-IA (BMP receptor subunit), BMPR-IB, and BMPR-II, and the BMP antagonists, noggin, gremlin, chordin, and follistatin was found when neurons first appear in the primordial bowel at embryonic day 12 (E12). Agonists, receptors, and antagonists were detected in separated populations of neural crestand noncrest-derived cells. When applied to immunopurified E12 ENS precursors, BMP-2 and BMP-4 induced nuclear translocation of phosphorylated Smad-1 (Sma and Mad-related protein). The number of neurons developing from these cells was increased by low concentrations and decreased by high concentrations of BMP-2 or BMP-4. BMPs induced the precocious appearance of TrkC-expressing neurons and their dependence on neurotrophin-3 for survival. BMP-4 interacted with glial cell line-derived neurotrophic factor (GDNF) to enhance neuronal development but limited GDNF-driven expansion of the precursor pool. BMPs also promoted development of smooth muscle from mesenchymal cells immunopurified at E12. To determine the physiological significance of these observations, the BMP antagonist noggin was overexpressed in the developing ENS of transgenic mice under the control of the neuron-specific enolase promoter. Neuronal numbers in both enteric plexuses and smooth muscle were increased throughout the postnatal small intestine. These increases were already apparent by E18. In contrast, TrkC-expressing neurons decreased in both plexuses of postnatal nogginoverexpressing animals, again an effect detectable at E18. BMP-2 and/or BMP-4 thus limit the size of the ENS but promote the development of specific subsets of enteric neurons, including those that express TrkC.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Enteric Neuronal Hyperplasia Occurs In Mice That Overexpressmentioning

confidence: 99%

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Bone Morphogenetic Protein-2 and -4 Limit the Number of Enteric Neurons But Promote Development of a TrkC-Expressing Neurotrophin-3-Dependent Subset

Chalazonitis¹,

D’Autréaux²,

Guha³

et al. 2004

J. Neurosci.

121

212

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“…Ptc mes/mes were produced as described by Makino et al (13). K14-Noggin were produced as described by Guha et al (37).…”

Section: Methodsmentioning

confidence: 99%

A role for suppressed incisor cuspal morphogenesis in the evolution of mammalian heterodont dentition

Ohazama

Blackburn

Porntaveetus

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

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Changes in tooth shape have played a major role in vertebrate evolution with modification of dentition allowing an organism to adapt to new feeding strategies. The current view is that molar teeth evolved from simple conical teeth, similar to canines, by progressive addition of extra "cones" to form progressively complex multicuspid crowns. Mammalian incisors, however, are neither conical nor multicuspid, and their evolution is unclear. We show that hypomorphic mutation of a cell surface receptor, Lrp4, which modulates multiple signaling pathways, produces incisors with grooved enamel surfaces that exhibit the same molecular characteristics as the tips of molar cusps. Mice with a null mutation of Lrp4 develop extra cusps on molars and have incisors that exhibit clear molar-like cusp and root morphologies. Molecular analysis identifies misregulation of Shh and Bmp signaling in the mutant incisors and suggests an uncoupling of the processes of tooth shape determination and morphogenesis. Incisors thus possess a developmentally suppressed, cuspid crown-like morphogenesis program similar to that in molars that is revealed by loss of Lrp4 activity. Several mammalian species naturally possess multicuspid incisors, suggesting that mammals have the capacity to form multicuspid teeth regardless of location in the oral jaw. Localized loss of enamel may thus have been an intermediary step in the evolution of cusps, both of which use Lrp4-mediated signaling.V ertebrates exhibit remarkable diversity in their dentitions, which is a feature of the importance of tooth shape in adaptation to new feeding strategies in evolution. Even quite closely related species of mammals can have different shapes of teeth and thus tooth development provides an excellent model for molecularly based evolutionary developmental biological studies (evo/devo). These tooth evolutional changes took place by the activation or inactivation of gene function, and thus evolutionary lost structures or gene activation/inactivation during evolution are occasionally retained as vestigial structures or latent gene activation/inactivation at embryonic stages.The current view is that all mammalian teeth evolved from simple ancestral teeth with a conical shape not dissimilar to mammalian canines (1). Mammalian heterodont dentitions contain a variety of tooth shapes and most evo/devo studies have focused solely on the molar dentition, with cuspal morphology being used as the main comparative feature between specimens (1). A cusp is a pointed or rounded projection of the tooth that is composed of both enamel and dentin, and the general consensus is that multicuspid teeth (molariform) evolved from conical teeth by progressive addition of extra "cones" (1). Incisors however are a uniquely mammalian tooth type that are neither conical nor multicuspid and their evolutional process is not understood.Among mammalian teeth, murine dentition has been used as a powerful tool for evo/devo studies because of the relative ease of gene manipulation. A major defining feature of R...

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“…2 Bone morphogenetic proteins (BMPs), members of the transforming growth factor-b subfamily, have been implicated in nervous system development and survival of peripheral neurons. [3][4][5] There are at least 20 structurally distinct BMPs. BMP2, BMP4, BMP6 and BMP7 are expressed at the early stage of brain development in vertebrates.…”

Section: Introductionmentioning

confidence: 99%

Adenoviral gene transfer of bone morphogenetic protein-7 enhances functional recovery after sciatic nerve injury in rats

Pan

et al. 2010

Gene Ther

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Bone morphogenetic proteins (BMPs), members of the transforming growth factor-b subfamily, function as instructive signals for neuronal lineage commitment and promote neuronal differentiation. However, the mechanism of BMP7 action in vivo after peripheral nerve injury is poorly understood. This study examines the efficacy of gene transfer of adenoviral (Ad) BMP7 on peripheral neuropathy. Transgene expression was found in both Ad-infected sciatic nerves and their respective remote neurons, indicating Ad transduction by a retrograde transport. After AdBMP7 infection to nerves, the sciatic nerves were crushed or transected. Hind limb functional behavior, including rotarod test and sciatic functional index, were conducted in rats weekly after nerve injury. Interestingly, enhanced BMP7 expression significantly improved hind limb functional recovery in AdBMP7-transduced rats when compared with AdGFPtransduced nerve-crushed or transected rats. Furthermore, AdBMP7 transduction reduced injury-induced macrophage activation, nerve demyelination and axonal degeneration. By contrast, AdBMP7 infection did not affect the hyperalgesia paw-withdrawal latency after nerve injury. We further examined the effect of AdBMP7 infection on sciatic nerve explant and Schwann cell cultures. Enhanced cell proliferation was significantly increased by AdBMP7 transduction in both cultures. Taken together, BMP7 overexpression by Ad gene transfer was beneficial in both nerves and Schwann cells on functional recovery after sciatic nerve injury in rats.

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Target-derived BMP signaling limits sensory neuron number and the extent of peripheral innervation in vivo

Cited by 69 publications

References 66 publications

Bone Morphogenetic Protein-2 and -4 Limit the Number of Enteric Neurons But Promote Development of a TrkC-Expressing Neurotrophin-3-Dependent Subset

Bone Morphogenetic Protein-2 and -4 Limit the Number of Enteric Neurons But Promote Development of a TrkC-Expressing Neurotrophin-3-Dependent Subset

A role for suppressed incisor cuspal morphogenesis in the evolution of mammalian heterodont dentition

Adenoviral gene transfer of bone morphogenetic protein-7 enhances functional recovery after sciatic nerve injury in rats

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